Pharmacokinetics of para-Aminosalicylic Acid Granules Under Four Dosing Conditions (original) (raw)
2001, The Annals of Pharmacotherapy
p ara-Aminosalicylic acid (PAS) is a second-line antimycobacterial agent that is generally reserved for patients with multidrug-resistant tuberculosis (MDR-TB) or patients intolerant to first-line drugs including isoniazid, rifampin, pyrazinamide, and ethambutol. 1,2 The major doselimiting adverse effect of PAS is gastrointestinal intolerance including nausea, vomiting, abdominal cramping, and diarrhea. In 1995, the Food and Drug Administration (FDA) approved a granule formulation of PAS that was designed to improve the gastrointestinal tolerance of PAS. Limited information exists in the literature regarding the pharmacokinetic profile of the PAS granules in healthy volunteers or in patients with MDR-TB, especially when combined with other antimycobacterial agents. We previously reported 3 a single-dose, single-drug pharmacokinetic evaluation of PAS 4-g granules in healthy volunteers and an extended dosing interval (twice and once daily) pharmacokinetic study of PAS 4-g granules in patients with tuberculosis. 4 However, the effects of various dosing conditions (e.g., intake of food, fruit juice, antacids, change in gastric pH) have not been examined in a crossover study. Food reduced the maximum concentration (C max) of isoniazid by 51% and that of rifampin by 36%, while antacids significantly reduced the absorption of ethambutol. 5-7 This study was conducted to determine pharmacokinetic parameter
Related papers
The Journal of Clinical Pharmacology, 2019
p ara-Aminosalicylic acid (PAS) is a second-line antimycobacterial agent that is generally reserved for patients with multidrug-resistant tuberculosis (MDR-TB) or patients intolerant to first-line drugs including isoniazid, rifampin, pyrazinamide, and ethambutol. 1,2 The major doselimiting adverse effect of PAS is gastrointestinal intolerance including nausea, vomiting, abdominal cramping, and diarrhea. In 1995, the Food and Drug Administration (FDA) approved a granule formulation of PAS that was designed to improve the gastrointestinal tolerance of PAS. Limited information exists in the literature regarding the pharmacokinetic profile of the PAS granules in healthy volunteers or in patients with MDR-TB, especially when combined with other antimycobacterial agents. We previously reported 3 a single-dose, single-drug pharmacokinetic evaluation of PAS 4-g granules in healthy volunteers and an extended dosing interval (twice and once daily) pharmacokinetic study of PAS 4-g granules in patients with tuberculosis. 4 However, the effects of various dosing conditions (e.g., intake of food, fruit juice, antacids, change in gastric pH) have not been examined in a crossover study. Food reduced the maximum concentration (C max) of isoniazid by 51% and that of rifampin by 36%, while antacids significantly reduced the absorption of ethambutol. 5-7 This study was conducted to determine pharmacokinetic parameter
Applied Clinical Pharmacokinetics
Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The author and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the author nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs.
Basic Pharmacokinetics Michael C. Makoid, Ph.D. Phillip J. Vuchetich, Pharm.D. Candidate
When I first started teaching, I had the good fortune to work with another new Ph.D., John Cobby. We struggled through our first five years on the otherside of the podium together and learned many of the tenents upon which this book is based, not content but process. First and formost, it was his belief that students are bright, enthusiastic and hardworking. We should tell them what to do and get out of their way. We both prepared extensive handouts complete with even more extensive practice problems so that the student could experience the scientific method as a detective might solve a murder mystery. The idea was to make learning pharmaceutical science interesting and fun. Through the years, as the methods became more refined, student perceptions and performance improved dramatically.
Basic pharmacokinetics Soraya Dhillon and Kiren Gill
Aims and learning outcomes Pharmacokinetics is a fundamental scientific discipline that underpins applied therapeutics. Patients need to be prescribed appropriate medicines for a clinical condition. The medicine is chosen on the basis of an evidence based approach to clinical practice and assured to be compatible with any other medicines or alternative therapies the patient may be taking. The design of a dosage regimen is dependent on a basic understanding of the drug use process (DUP). When faced with a patient who shows specific clinical signs and symptoms, pharmacists must always ask a fundamental question: ‘Is this patient suffering from a drug-relatedproblem?’ Once this issue is evaluated and a clinical diagnosis is available, the pharmacist can apply the DUP to ensure that the patient is prescribed an appropriate medication regimen, that the patient understands the therapy prescribed, and that an agreed concordance plan is achieved.
Absorption Drug Body Cell membrane Passive diffusion Facilitated diffusion Aqueous channels Active transport Drug associated factors Ionization state (ionized= H2O soluble; non-ionized=lipid soluble) MW Solubility (lipophilicity) Formulation Px associated factors Gastric emptying Stomach acidity Blood flow to GI tract Distribution Membrane permeability (↑lipophilicity= ↑permeability) BBB, BTB, BPB Plasma protein binding Albumin: binds to acidic drugs α1 acid glycoprotein: for basic drugs Depot storage (accumulation of lipophilic drugs in fat) Apparent volume of distribution (Vd= dose/C º ) Correlates Dose with plasma levels at t=0 ↑Vd=↓ [plasma] ↑plasma protein binding= ↓Vd Metabolism Biotransformation: Active drug less active (or inactive form) Inactive/less active active form • Phase I reactions(nonsynthetic): Drug polar (H2O soluble) Oxidation, reduction, deamination, hydrolysis • Phase II reactions (synthetic): conjugation of polar group Glucuronate, Acetate, GSH, Gly, SO4, -CH3 groups Sites of metabolism: Liver Kidneys Blood Intestinal walls Metabolism cont'd Determinants of Biotransformation rate Genetics Hydrolysis of esters Acetylation of amines Oxidation Other drugs Ez induction Ez inhibition Inhibition of intestinal P-glycoprotein (Digoxin, cyclosporine, saquinavir)
Loading Preview
Sorry, preview is currently unavailable. You can download the paper by clicking the button above.