Bruce Aungst - Academia.edu (original) (raw)

Papers by Bruce Aungst

Research paper thumbnail of Prodrugs for improved oral nalbuphine bioavailability: inter-species differences in the disposition of nalbuphine and its acetylsalicylate and anthranilate esters

International Journal of Pharmaceutics, 1987

... inter-species differences in the disposition of nalbuphine and its acetylsalicylate and anthr... more ... inter-species differences in the disposition of nalbuphine and its acetylsalicylate and anthranilate esters Bruce J. Aungst, Melvyn J. Myers, Ell ... Prodrugs improved the oral bioavailability of other phenols and catechols including etilefrine (Wagner et al-, 1980), L-DOPA (Bodor et al ...

Research paper thumbnail of Prodrug and analog approaches to improving the intestinal absorption of a cyclic peptide, GPIIb/IIIa receptor antagonist

Pharmaceutical Research, Aug 1, 1997

Research paper thumbnail of Trandermal delivery of opioids

Research paper thumbnail of Use of prodrugs of 3-hydroxymorphinans to prevent bitter taste upon buccal, nasal or sublingual administration

Research paper thumbnail of Substituted Benzoate Ester Prodrugs of Estrogens

Research paper thumbnail of The effect of dose on the disposition of lead in rats after intravenous and oral administration

Toxicology and Applied Pharmacology, 1981

Research paper thumbnail of Introduction: Pharmaceutics and drug delivery

Research paper thumbnail of Restricted Intestinal Absorption of Some β-Lactam Antibiotics by an Energy-Dependent Efflux System in Rat Intestine

Pharmaceutical Research, 1997

Purpose. The purpose of this study was to examine factors limiting the intestinal absorption of o... more Purpose. The purpose of this study was to examine factors limiting the intestinal absorption of orally inactive ß-lactam antibiotics.

Research paper thumbnail of Beta-cyclodextrin as a suitable solubilizing agent for in situ absorption study of poorly water-soluble drugs

International journal of pharmaceutics, Jan 6, 2004

To evaluate the intestinal permeability of poorly water-soluble compounds, it is of importance to... more To evaluate the intestinal permeability of poorly water-soluble compounds, it is of importance to completely dissolve them in a medium and to avoid precipitation during experiments. This study was undertaken to find an agent possessing a high-solubilizing capacity and exhibiting minimal modulating impact on membrane integrity and absorption systems such as passive diffusion and carrier-mediated permeation. Phenytoin dissolution was compared in the presence of seven solubilizing agents at concentrations of 1, 2, or 5% using a centrifugation method. The capacity to dissolve phenytoin was great in beta-cyclodextrin (beta-CD) and hydroxypropyl beta-cyclodextrin, followed by Tween 80. Those of methanol, dimethyl sulfoxide, dimethyl acetoamide, and polyethylene glycol 400 were much lower than expected. One percent beta-CD did not alter the absorption of fluorescein isothiocyanate-dextran 4,000 or the release of protein and lactate dehydrogenase into in situ loop contents, suggesting that ...

Research paper thumbnail of Prodrugs for improved oral beta-estradiol bioavailability

Pharmaceutical research, 1988

Prodrugs of beta-estradiol (1) were prepared with the objective of improving its oral bioavailabi... more Prodrugs of beta-estradiol (1) were prepared with the objective of improving its oral bioavailability. beta-Estradiol-3-acetylsalicylate (2), beta-estradiol-3-salicylate (3), and beta-estradiol-3-anthranilate (4) were synthesized. With these prodrugs the 3-phenolic hydroxy group of estradiol was protected, so that first-pass conjugative metabolism could be reduced. Prodrug hydrolysis rates in dog and human plasma in vitro were determined. Deacetylation of estradiol-3-acetylsalicylate was much more rapid than its hydrolysis to estradiol. In dogs, oral estradiol bioavailability after administration of 2 and 4 was 17-fold and 5-fold higher, respectively, than after oral 1.

Research paper thumbnail of Effects of plasma protein binding displacement on the pharmacokinetics, tissue and tumor concentrations and efficacy of brequinar, a highly protein-bound antitumor agent

The Journal of pharmacology and experimental therapeutics, 1990

Brequinar is a developmental antitumor agent which is highly bound to plasma proteins. The effect... more Brequinar is a developmental antitumor agent which is highly bound to plasma proteins. The effects of plasma protein binding displacement on brequinar pharmacokinetics, tissue distribution, tumor distribution and antitumor efficacy were evaluated. Sodium salicylate and ibuprofen increased the percentage of free brequinar in serum in vitro, in proportion to their added concentrations. Sodium salicylate also altered the pharmacokinetics of i.v. brequinar in rats when adminstered i.v. or p.o. at 10- or 50-fold higher doses than brequinar. At the highest salicylate/brequinar dose ratio, significant increases were observed for terminal half-life, mean residence times in the body and tissues, systemic clearance, distribution clearance, the volume of the central compartment and volume of distribution at steady state. Neither salicylate nor ibuprofen increased brequinar concentrations in lung and muscle specimens from rats, 4 or 24 hr after dosing. Tumor, lung and muscle brequinar concentra...

Research paper thumbnail of The Influence of Donor and Reservoir Additives on Caco-2 Permeability and Secretory Transport of HIV Protease Inhibitors and Other Lipophilic Compounds

Pharmaceutical Research, 2000

Purpose. To optimize the conditions for determining Caco-2 permeation of HIV protease inhibitors ... more Purpose. To optimize the conditions for determining Caco-2 permeation of HIV protease inhibitors and other lipophilic compounds, and to compare cyclic urea HIV protease inhibitors with marketed compounds.

Research paper thumbnail of Kinetic characterization of in vitro lead transport across the rat small intestine

Toxicology and Applied Pharmacology, 1981

Lead transport through the everted rat small intestine was used as an in vitro model to examine t... more Lead transport through the everted rat small intestine was used as an in vitro model to examine the kinetics and mechanism of gastrointestinal lead absorption. Mucosal-to-serosal lead flux increased nonlinearly with increasing mucosal lead concentrations (0.5-48.3 PM), and an apparent capacity-limited lead flux was observed with intestines of both adult and adolescent rats. Uptake of lead by the adult intestinal tissue, measured at the end of the flux experiments, was also nonlinearly related to mucosal lead concentration. Both intestinal uptake and mucosal-to-serosal flux were reduced by anoxia and by inhibition of glycolysis using fluoride. The data were consistent with a model of lead intestinal transport which included both a carrier-mediated component and passive diffusion. Kinetic parameters for these transport processes were obtained. The relative contribution of passive diffusion to total lead llux increased with increasing lead concentration, but was quantitatively minor (~20%) at all lead concentrations tested. The apparent capacity-limited component of lead flux was not due artifactually to reduced lead solubility in the mucosal solution at high metal concentrations, nor was it due apparently to reduced viability of the intestinal tissue, since lead did not alter 3-Gmethylglucose transport over the range of lead concentration used. When the same lead solution was placed on both sides of an everted intestine, net serosal-tomucosal lead flux was observed at low lead concentrations. It is therefore likely that intestinal lead transport may be bidirectional, similar to calcium transport.

Research paper thumbnail of Prodrugs for Improved Oral β-Estradiol Bioavailability

Pharmaceutical Research - PHARMACEUT RES, 1988

Prodrugs of ß-estradiol (1) were prepared with the objective of improving its oral bioavailabilit... more Prodrugs of ß-estradiol (1) were prepared with the objective of improving its oral bioavailability. ß-Estradiol-3-acetylsalicylate (2), ß-estradiol-3-salicylate (3), and ß-estradiol-3-anthranilate (4) were synthesized. With these prodrugs the 3-phenolic hydroxy group of estradiol was protected, so that first-pass conjugative metabolism could be reduced. Prodrug hydrolysis rates in dog and human plasma in vitro were determined. Deacetylation of estradiol-3-acetylsalicylate was much more rapid than its hydrolysis to estradiol. In dogs, oral estradiol bioavailability after administration of 2 and 4 was 17-fold and 5-fold higher, respectively, than after oral 1.

Research paper thumbnail of Effects of a Nonabsorbable Chelating Resin on Lead Absorption, Elimination, and Accumulation in the Rat

Pharmacology, 1982

In rats, oral administration of lead-chelating resin (Chelex-100) reduced the absorption of an or... more In rats, oral administration of lead-chelating resin (Chelex-100) reduced the absorption of an oral lead dose (10 mg/kg) when both doses were given at approximately the same time. The same oral resin did not reduce blood lead concentrations when administered after the lead dose had been absorbed or after systemic lead administration (1 mg/kg, intracardiac), indicating that the resin did not influence lead elimination. As a dietary supplement the resin was also ineffective in reducing blood and kidney lead concentrations in rats exposed to lead in drinking water. Thus, the possible therapeutic uses of this lead-chelating resin may be limited.

Research paper thumbnail of Relationship Between Loperamide-Induced Sedative Effect and Digoxin Pharmacokinetics in Healthy Japanese Subjects

Pharmaceutical Research, 2005

Loperamide-induced suppressive effects on central nervous system closely relate to a lack of or d... more Loperamide-induced suppressive effects on central nervous system closely relate to a lack of or decline in the P-glycoprotein (P-gp) function. The aim of this study was to determine the loperamide-induced sedative effect quantitatively and to investigate possible alterations in the pharmacokinetics of digoxin, a substrate for P-gp, in Japanese subjects. Loperamide hydrochloride (2 mg) was administered orally to 26 subjects and the critical flicker-fusion frequency threshold (CFF) values were measured every 30 min separately by portable instrument. Further, digoxin (0.25 mg) was administered to 8 subjects, and the plasma concentration was determined. In five subjects who complained of drowsiness, the CFF values more remarkably decreased compared with those in the other subjects. The Tmax and mean residence time (MRT) values of digoxin pharmacokinetics in four subjects with drowsiness were significantly lower and Cmax was higher than those in four subjects with marginal effect. Moreover, there were good correlations between the CFF value-time profile and the Cmax, Tmax, and MRT of digoxin. The determination of the CFF value after oral administration of loperamide will be useful for evaluating varied P-gp function and for anticipating individual variations in the disposition of P-gp substrates in humans.

Research paper thumbnail of Buccal and Oral Bioavailability of Nalbuphine in Rats

Journal of Pharmaceutical Sciences, 1986

Skip to Main Content. ...

Research paper thumbnail of Formulation and food effects on the oral absorption of a poorly water soluble, highly permeable antiretroviral agent

Journal of Pharmaceutical Sciences, 2002

DPC 961 is a low-solubility, high-permeability, second-generation non-nucleoside reverse transcri... more DPC 961 is a low-solubility, high-permeability, second-generation non-nucleoside reverse transcriptase inhibitor. The purpose of these studies was to evaluate the effects of drug substance and formulation variables on DPC 961 oral absorption, and to compare fed and fasted state oral absorption. To accomplish this, groups of four to six dogs were dosed with various formulations of DPC 961 under fasted or fed conditions, and DPC 961 pharmacokinetics were examined. Absolute oral bioavailability, based on i.v. AUC in the same dogs, was 24% after a suspension dose in fasted dogs and was 51% in fed dogs. Bioavailability with an unoptimized tablet formulation was 30% in fasted dogs and 86% in fed dogs. DPC 961 oral absorption was shown to be dependent on drug substance particle size in fasted dogs, after dosing with a tablet formulation where only the drug substance particle size was varied, but there was no difference in fed dogs. AUC and C(max) increased in proportion with increases in tablet strength from 100 to 400 mg, using tablets manufactured from a common granulation. Tablets made with 50 and 66% drug loadings showed similar relative oral bioavailabilities. Tablets prepared with two different polymorphic forms of DPC 961 were also compared, and these were found to be equivalent. These studies provided a useful component of the formulation development process, to help identify and control the variables affecting oral absorption of this potential new therapeutic agent.

Research paper thumbnail of Inhibition of Oral Lead Absorption in Rats by Phosphate-Containing Products

Journal of Pharmaceutical Sciences, 1983

Recent studies indicate that elevated blood lead levels in children are largely a result of expos... more Recent studies indicate that elevated blood lead levels in children are largely a result of exposure to this metal via the oral route. A logical approach to decrease or prevent lead intoxication would be to reduce its absorption as soon as lead ingestion is known or suspected. Presently, however, there are no readily available products recommended to accomplish this goal. It was found that a phosphate-buffered, saline laxative reduced lead absorption over 50% in rats administered a single oral lead acetate dose, presumably by promoting the formation of less soluble lead salts. A popular phosphate-containing carbonated beverage also decreased lead absorption approximately 30% after oral lead acetate or lead-based paint doses, possibly by decreasing solubility, dissolution rate and/or GI motility. It is possible that these household products, and those with similar ingredients, may be safely used to reduce lead absorption in humans.

Research paper thumbnail of Criteria for selecting pharmacokinetic repeat study samples

Bioanalysis, 2009

The pharmacokinetic (PK) repeat study sample, selected by the study pharmacokineticist, requires ... more The pharmacokinetic (PK) repeat study sample, selected by the study pharmacokineticist, requires repeat bioanalysis because the concentration is incongruous with drug plasma concentration versus time profile. The inconsistency could be due to a number of reasons, including the detectable drug concentration in a predose sample or a sample from a placebo control group or a significant double peak in the terminal phase of an individual plasma concentration versus time profile that is not consistent with the profiles from other subjects in the same dose group. The justification for selecting the PK repeat sample should be clearly documented. The repeat analysis should be conducted in duplicate or triplicate as allowed by sample volume. To avoid subjectively selecting PK repeat samples, standard operating procedures should be prepared prior to the start of the study in order to define the criteria for selecting PK repeat study samples and also the procedure for conducting repeat analysis...

Research paper thumbnail of Prodrugs for improved oral nalbuphine bioavailability: inter-species differences in the disposition of nalbuphine and its acetylsalicylate and anthranilate esters

International Journal of Pharmaceutics, 1987

... inter-species differences in the disposition of nalbuphine and its acetylsalicylate and anthr... more ... inter-species differences in the disposition of nalbuphine and its acetylsalicylate and anthranilate esters Bruce J. Aungst, Melvyn J. Myers, Ell ... Prodrugs improved the oral bioavailability of other phenols and catechols including etilefrine (Wagner et al-, 1980), L-DOPA (Bodor et al ...

Research paper thumbnail of Prodrug and analog approaches to improving the intestinal absorption of a cyclic peptide, GPIIb/IIIa receptor antagonist

Pharmaceutical Research, Aug 1, 1997

Research paper thumbnail of Trandermal delivery of opioids

Research paper thumbnail of Use of prodrugs of 3-hydroxymorphinans to prevent bitter taste upon buccal, nasal or sublingual administration

Research paper thumbnail of Substituted Benzoate Ester Prodrugs of Estrogens

Research paper thumbnail of The effect of dose on the disposition of lead in rats after intravenous and oral administration

Toxicology and Applied Pharmacology, 1981

Research paper thumbnail of Introduction: Pharmaceutics and drug delivery

Research paper thumbnail of Restricted Intestinal Absorption of Some β-Lactam Antibiotics by an Energy-Dependent Efflux System in Rat Intestine

Pharmaceutical Research, 1997

Purpose. The purpose of this study was to examine factors limiting the intestinal absorption of o... more Purpose. The purpose of this study was to examine factors limiting the intestinal absorption of orally inactive ß-lactam antibiotics.

Research paper thumbnail of Beta-cyclodextrin as a suitable solubilizing agent for in situ absorption study of poorly water-soluble drugs

International journal of pharmaceutics, Jan 6, 2004

To evaluate the intestinal permeability of poorly water-soluble compounds, it is of importance to... more To evaluate the intestinal permeability of poorly water-soluble compounds, it is of importance to completely dissolve them in a medium and to avoid precipitation during experiments. This study was undertaken to find an agent possessing a high-solubilizing capacity and exhibiting minimal modulating impact on membrane integrity and absorption systems such as passive diffusion and carrier-mediated permeation. Phenytoin dissolution was compared in the presence of seven solubilizing agents at concentrations of 1, 2, or 5% using a centrifugation method. The capacity to dissolve phenytoin was great in beta-cyclodextrin (beta-CD) and hydroxypropyl beta-cyclodextrin, followed by Tween 80. Those of methanol, dimethyl sulfoxide, dimethyl acetoamide, and polyethylene glycol 400 were much lower than expected. One percent beta-CD did not alter the absorption of fluorescein isothiocyanate-dextran 4,000 or the release of protein and lactate dehydrogenase into in situ loop contents, suggesting that ...

Research paper thumbnail of Prodrugs for improved oral beta-estradiol bioavailability

Pharmaceutical research, 1988

Prodrugs of beta-estradiol (1) were prepared with the objective of improving its oral bioavailabi... more Prodrugs of beta-estradiol (1) were prepared with the objective of improving its oral bioavailability. beta-Estradiol-3-acetylsalicylate (2), beta-estradiol-3-salicylate (3), and beta-estradiol-3-anthranilate (4) were synthesized. With these prodrugs the 3-phenolic hydroxy group of estradiol was protected, so that first-pass conjugative metabolism could be reduced. Prodrug hydrolysis rates in dog and human plasma in vitro were determined. Deacetylation of estradiol-3-acetylsalicylate was much more rapid than its hydrolysis to estradiol. In dogs, oral estradiol bioavailability after administration of 2 and 4 was 17-fold and 5-fold higher, respectively, than after oral 1.

Research paper thumbnail of Effects of plasma protein binding displacement on the pharmacokinetics, tissue and tumor concentrations and efficacy of brequinar, a highly protein-bound antitumor agent

The Journal of pharmacology and experimental therapeutics, 1990

Brequinar is a developmental antitumor agent which is highly bound to plasma proteins. The effect... more Brequinar is a developmental antitumor agent which is highly bound to plasma proteins. The effects of plasma protein binding displacement on brequinar pharmacokinetics, tissue distribution, tumor distribution and antitumor efficacy were evaluated. Sodium salicylate and ibuprofen increased the percentage of free brequinar in serum in vitro, in proportion to their added concentrations. Sodium salicylate also altered the pharmacokinetics of i.v. brequinar in rats when adminstered i.v. or p.o. at 10- or 50-fold higher doses than brequinar. At the highest salicylate/brequinar dose ratio, significant increases were observed for terminal half-life, mean residence times in the body and tissues, systemic clearance, distribution clearance, the volume of the central compartment and volume of distribution at steady state. Neither salicylate nor ibuprofen increased brequinar concentrations in lung and muscle specimens from rats, 4 or 24 hr after dosing. Tumor, lung and muscle brequinar concentra...

Research paper thumbnail of The Influence of Donor and Reservoir Additives on Caco-2 Permeability and Secretory Transport of HIV Protease Inhibitors and Other Lipophilic Compounds

Pharmaceutical Research, 2000

Purpose. To optimize the conditions for determining Caco-2 permeation of HIV protease inhibitors ... more Purpose. To optimize the conditions for determining Caco-2 permeation of HIV protease inhibitors and other lipophilic compounds, and to compare cyclic urea HIV protease inhibitors with marketed compounds.

Research paper thumbnail of Kinetic characterization of in vitro lead transport across the rat small intestine

Toxicology and Applied Pharmacology, 1981

Lead transport through the everted rat small intestine was used as an in vitro model to examine t... more Lead transport through the everted rat small intestine was used as an in vitro model to examine the kinetics and mechanism of gastrointestinal lead absorption. Mucosal-to-serosal lead flux increased nonlinearly with increasing mucosal lead concentrations (0.5-48.3 PM), and an apparent capacity-limited lead flux was observed with intestines of both adult and adolescent rats. Uptake of lead by the adult intestinal tissue, measured at the end of the flux experiments, was also nonlinearly related to mucosal lead concentration. Both intestinal uptake and mucosal-to-serosal flux were reduced by anoxia and by inhibition of glycolysis using fluoride. The data were consistent with a model of lead intestinal transport which included both a carrier-mediated component and passive diffusion. Kinetic parameters for these transport processes were obtained. The relative contribution of passive diffusion to total lead llux increased with increasing lead concentration, but was quantitatively minor (~20%) at all lead concentrations tested. The apparent capacity-limited component of lead flux was not due artifactually to reduced lead solubility in the mucosal solution at high metal concentrations, nor was it due apparently to reduced viability of the intestinal tissue, since lead did not alter 3-Gmethylglucose transport over the range of lead concentration used. When the same lead solution was placed on both sides of an everted intestine, net serosal-tomucosal lead flux was observed at low lead concentrations. It is therefore likely that intestinal lead transport may be bidirectional, similar to calcium transport.

Research paper thumbnail of Prodrugs for Improved Oral β-Estradiol Bioavailability

Pharmaceutical Research - PHARMACEUT RES, 1988

Prodrugs of ß-estradiol (1) were prepared with the objective of improving its oral bioavailabilit... more Prodrugs of ß-estradiol (1) were prepared with the objective of improving its oral bioavailability. ß-Estradiol-3-acetylsalicylate (2), ß-estradiol-3-salicylate (3), and ß-estradiol-3-anthranilate (4) were synthesized. With these prodrugs the 3-phenolic hydroxy group of estradiol was protected, so that first-pass conjugative metabolism could be reduced. Prodrug hydrolysis rates in dog and human plasma in vitro were determined. Deacetylation of estradiol-3-acetylsalicylate was much more rapid than its hydrolysis to estradiol. In dogs, oral estradiol bioavailability after administration of 2 and 4 was 17-fold and 5-fold higher, respectively, than after oral 1.

Research paper thumbnail of Effects of a Nonabsorbable Chelating Resin on Lead Absorption, Elimination, and Accumulation in the Rat

Pharmacology, 1982

In rats, oral administration of lead-chelating resin (Chelex-100) reduced the absorption of an or... more In rats, oral administration of lead-chelating resin (Chelex-100) reduced the absorption of an oral lead dose (10 mg/kg) when both doses were given at approximately the same time. The same oral resin did not reduce blood lead concentrations when administered after the lead dose had been absorbed or after systemic lead administration (1 mg/kg, intracardiac), indicating that the resin did not influence lead elimination. As a dietary supplement the resin was also ineffective in reducing blood and kidney lead concentrations in rats exposed to lead in drinking water. Thus, the possible therapeutic uses of this lead-chelating resin may be limited.

Research paper thumbnail of Relationship Between Loperamide-Induced Sedative Effect and Digoxin Pharmacokinetics in Healthy Japanese Subjects

Pharmaceutical Research, 2005

Loperamide-induced suppressive effects on central nervous system closely relate to a lack of or d... more Loperamide-induced suppressive effects on central nervous system closely relate to a lack of or decline in the P-glycoprotein (P-gp) function. The aim of this study was to determine the loperamide-induced sedative effect quantitatively and to investigate possible alterations in the pharmacokinetics of digoxin, a substrate for P-gp, in Japanese subjects. Loperamide hydrochloride (2 mg) was administered orally to 26 subjects and the critical flicker-fusion frequency threshold (CFF) values were measured every 30 min separately by portable instrument. Further, digoxin (0.25 mg) was administered to 8 subjects, and the plasma concentration was determined. In five subjects who complained of drowsiness, the CFF values more remarkably decreased compared with those in the other subjects. The Tmax and mean residence time (MRT) values of digoxin pharmacokinetics in four subjects with drowsiness were significantly lower and Cmax was higher than those in four subjects with marginal effect. Moreover, there were good correlations between the CFF value-time profile and the Cmax, Tmax, and MRT of digoxin. The determination of the CFF value after oral administration of loperamide will be useful for evaluating varied P-gp function and for anticipating individual variations in the disposition of P-gp substrates in humans.

Research paper thumbnail of Buccal and Oral Bioavailability of Nalbuphine in Rats

Journal of Pharmaceutical Sciences, 1986

Skip to Main Content. ...

Research paper thumbnail of Formulation and food effects on the oral absorption of a poorly water soluble, highly permeable antiretroviral agent

Journal of Pharmaceutical Sciences, 2002

DPC 961 is a low-solubility, high-permeability, second-generation non-nucleoside reverse transcri... more DPC 961 is a low-solubility, high-permeability, second-generation non-nucleoside reverse transcriptase inhibitor. The purpose of these studies was to evaluate the effects of drug substance and formulation variables on DPC 961 oral absorption, and to compare fed and fasted state oral absorption. To accomplish this, groups of four to six dogs were dosed with various formulations of DPC 961 under fasted or fed conditions, and DPC 961 pharmacokinetics were examined. Absolute oral bioavailability, based on i.v. AUC in the same dogs, was 24% after a suspension dose in fasted dogs and was 51% in fed dogs. Bioavailability with an unoptimized tablet formulation was 30% in fasted dogs and 86% in fed dogs. DPC 961 oral absorption was shown to be dependent on drug substance particle size in fasted dogs, after dosing with a tablet formulation where only the drug substance particle size was varied, but there was no difference in fed dogs. AUC and C(max) increased in proportion with increases in tablet strength from 100 to 400 mg, using tablets manufactured from a common granulation. Tablets made with 50 and 66% drug loadings showed similar relative oral bioavailabilities. Tablets prepared with two different polymorphic forms of DPC 961 were also compared, and these were found to be equivalent. These studies provided a useful component of the formulation development process, to help identify and control the variables affecting oral absorption of this potential new therapeutic agent.

Research paper thumbnail of Inhibition of Oral Lead Absorption in Rats by Phosphate-Containing Products

Journal of Pharmaceutical Sciences, 1983

Recent studies indicate that elevated blood lead levels in children are largely a result of expos... more Recent studies indicate that elevated blood lead levels in children are largely a result of exposure to this metal via the oral route. A logical approach to decrease or prevent lead intoxication would be to reduce its absorption as soon as lead ingestion is known or suspected. Presently, however, there are no readily available products recommended to accomplish this goal. It was found that a phosphate-buffered, saline laxative reduced lead absorption over 50% in rats administered a single oral lead acetate dose, presumably by promoting the formation of less soluble lead salts. A popular phosphate-containing carbonated beverage also decreased lead absorption approximately 30% after oral lead acetate or lead-based paint doses, possibly by decreasing solubility, dissolution rate and/or GI motility. It is possible that these household products, and those with similar ingredients, may be safely used to reduce lead absorption in humans.

Research paper thumbnail of Criteria for selecting pharmacokinetic repeat study samples

Bioanalysis, 2009

The pharmacokinetic (PK) repeat study sample, selected by the study pharmacokineticist, requires ... more The pharmacokinetic (PK) repeat study sample, selected by the study pharmacokineticist, requires repeat bioanalysis because the concentration is incongruous with drug plasma concentration versus time profile. The inconsistency could be due to a number of reasons, including the detectable drug concentration in a predose sample or a sample from a placebo control group or a significant double peak in the terminal phase of an individual plasma concentration versus time profile that is not consistent with the profiles from other subjects in the same dose group. The justification for selecting the PK repeat sample should be clearly documented. The repeat analysis should be conducted in duplicate or triplicate as allowed by sample volume. To avoid subjectively selecting PK repeat samples, standard operating procedures should be prepared prior to the start of the study in order to define the criteria for selecting PK repeat study samples and also the procedure for conducting repeat analysis...