Barry Woodcock - Academia.edu (original) (raw)
Papers by Barry Woodcock
Trends Pharmacol Sci, 1984
Trends Pharmacol Sci, 1983
Trends Pharmacol Sci, 1986
Arzneimittel-Forschung
ABSTRACT
ZFA. Zeitschrift für Allgemeinmedizin
Journal of Cardiovascular Pharmacology
Dihydroergotoxine plasma concentrations determined using a newly developed radioimmunoassay metho... more Dihydroergotoxine plasma concentrations determined using a newly developed radioimmunoassay method and corresponding blood-pressure-lowering effects have been measured in normotensive subjects after intravenous injection (0.6 mg) and administration of an oral solution (4.5 mg). Plasma concentrations in the range 0.2-1 ng/ml dihydroergotoxine produced clinically significant reductions of up to 15% in systolic and diastolic standing and supine blood pressures, while no significant changes occurred in pulse rate.
Arzneimittel-Forschung
For the quantitative and qualitative determination of dihydroergotoxine methanesulphonate (DCCK) ... more For the quantitative and qualitative determination of dihydroergotoxine methanesulphonate (DCCK) a radioimmunoassay was developed. This method involves use of an antibody against the dihydrolysergic acid moiety and an 125I-labelled dihydrolysergic tracer. The differentiation of dihydroergopeptides, lysergic acid and the ergopeptides was obtained by modification of extraction methods already published. The assay procedure detects around 10 pg/ml dihydroergotoxine. Dihydrolysergic acid and lysergic acid are not detectable up to about 6 ng/ml. Ergometrine and alpha-ergocryptine show cross-reactivities of 14% and 7.5%, respectively. All dihydroergopeptides included in dihydroergotoxine show the same cross-reactivity as dihydroergotoxine itself. Intra- and inter-assay variations were approximately 12% and 13%, respectively.
DMW - Deutsche Medizinische Wochenschrift
Arzneimittel-Forschung
8 patients with ventricular premature contractions were treated with prajmalium bitartrate (Neo-G... more 8 patients with ventricular premature contractions were treated with prajmalium bitartrate (Neo-Gilurytmal) 20 mg q.i.d. The electrocardiograms were continuously monitored by a computerized arrhythmia monitoring system. For definition of the drug's pharmacokinetic properties plasma concentrations were determined. 7 patients showed a marked arrhythmia reduction. Mean ventricular premature contraction frequency was significantly reduced 6 h after onset of treatment, maximum arrhythmia suppression to 34% of control was observed after 24 h of treatment. The correlation of antiarrhythmic response and plasma concentrations was good. Mean plasma concentrations during steady state conditions were 218 ng/ml. Plasma half-life was determined 7.3 h. The lower limit of therapeutic plasma concentrations was between 43 and 145 ng/ml. A mean total clearance of 344 ml/min indicates a low hepatic extraction of prajmalium bitartrate. Moreover, the distribution volume of 204 l suggests a high tissue affinity of the drug.
Arzneimittel-Forschung
Kidney independent glycosides offer a high measure of therapeutic safety in comparison with kidne... more Kidney independent glycosides offer a high measure of therapeutic safety in comparison with kidney dependent glycosides. The intoxication rate lies between 4 and 6%. The pharmacokinetic properties of pentaformylgitoxin (INN: gitoformate) are comparable with those for digitoxin. The active glycoside 16-formylgitoxin (INN: gitaloxin) is formed by rapid deformylation of the formyl residue on the sugar chain. The maintenance dose of 0.06 mg daily, based on the half-life, produces therapeutic concentrations in the range 6-30 ng/ml. The required loading dose, as for digitoxin, amounts to 10 times the maintenance dose.
DMW - Deutsche Medizinische Wochenschrift
ZFA. Zeitschrift für Allgemeinmedizin
International journal of clinical pharmacology, therapy, and toxicology
In a prospective randomized study 12 patients suffering from cirrhosis of the liver (stable phase... more In a prospective randomized study 12 patients suffering from cirrhosis of the liver (stable phase) and 12 healthy volunteers were treated daily with either 0.3 mg metildigoxin (Lanitop) or 0.4 mg beta-acetyldigoxin (Novodigal) orally. Every day the total serum digoxin concentrations of the patients and volunteers were measured by radioimmunoassay. Both digoxin and beta-methyldigoxin are measured by this method. In patients receiving metildigoxin therapy the ratio of beta-methyldigoxin/digoxin in the serum was determined by HPLC. The digoxin levels in patients with cirrhosis treated with metildigoxin were statistically significantly higher than in healthy volunteers. In patients with cirrhosis the proportion of serum beta-methyldigoxin averaged 77.7% of the total digoxin concentration, whereas the proportion was only 37.5% in healthy volunteers. With beta-acetyldigoxin there was no statistically significant difference between patients with cirrhosis and healthy volunteers. The higher total serum-digoxin levels in patients with cirrhosis of the liver after moderate saturation with metildigoxin are caused by reduced demethylation of beta-methyldigoxin to digoxin due to impaired liver function. A comparison with healthy volunteers showed that the reduced hepatic metabolism in the cirrhotic patients caused changes in the pharmacokinetics: a reduced metildigoxin clearance and a smaller distribution volume were found. According to our findings there is more danger of digitalis toxicity in patients with cirrhosis of the liver on a standard dosage of metildigoxin than on a standard dosage of beta-acetyldigoxin.
Arzneimittel-Forschung
The effect of beta-acetyldigoxin (Novodigal) on color vision in normal, healthy subjects was stud... more The effect of beta-acetyldigoxin (Novodigal) on color vision in normal, healthy subjects was studied using cortical evoked potentials. Initial results indicate a significant latency increase of one component of the visual evoked potential (VEP) and a dose dependency following a change of color from blue to red. The Farnsworth-Munsell-100-Hue test, however, showed no significant changes in color vision. It is postulated that the VEP is an even more sensitive measurement of color vision than subjective tests are.
International journal of clinical pharmacology, therapy, and toxicology
The relative bioavailability and plasma concentration profile of dihydroergotoxine as a solution,... more The relative bioavailability and plasma concentration profile of dihydroergotoxine as a solution, standard tablets and slow-release formulations have been compared in 12 healthy subjects following the application of 4-5 mg as a single dose or as 2-3 smaller dose units given at 5 h intervals. Plasma dihydroergotoxine concentrations were measured using a sensitive and highly specific radioimmunoassay procedure. The plasma concentration profile after a single 4.5 mg SR-capsule with relative bioavailability 92% (Oral solution, 4.5 mg as single dose = 100%), releasing 80% of the capsule contents within 8 h, was similar to that achieved following the application of 2-3 divided doses at 5 h intervals of a solution (relative bioavailability = 85%), standard tablet (relative bioavailability = 99%) or SR-tablets (relative bioavailability 78%). Slow-release formulations of dihydroergotoxine do not lead to high postdose concentrations as seen with solutions and standard tablets. Application of a single 4.5 mg SR-capsule can maintain prolonged plateau concentrations exceeding 100 pg/ml over 10 h. Reducing the rate of presentation of dihydroergotoxine to the body in the form of slow release formulations or by using spaced doses does not markedly affect bioavailability when compared to a solution.
International journal of clinical pharmacology and therapeutics
International journal of clinical pharmacology, therapy, and toxicology
Trends Pharmacol Sci, 1984
Trends Pharmacol Sci, 1983
Trends Pharmacol Sci, 1986
Arzneimittel-Forschung
ABSTRACT
ZFA. Zeitschrift für Allgemeinmedizin
Journal of Cardiovascular Pharmacology
Dihydroergotoxine plasma concentrations determined using a newly developed radioimmunoassay metho... more Dihydroergotoxine plasma concentrations determined using a newly developed radioimmunoassay method and corresponding blood-pressure-lowering effects have been measured in normotensive subjects after intravenous injection (0.6 mg) and administration of an oral solution (4.5 mg). Plasma concentrations in the range 0.2-1 ng/ml dihydroergotoxine produced clinically significant reductions of up to 15% in systolic and diastolic standing and supine blood pressures, while no significant changes occurred in pulse rate.
Arzneimittel-Forschung
For the quantitative and qualitative determination of dihydroergotoxine methanesulphonate (DCCK) ... more For the quantitative and qualitative determination of dihydroergotoxine methanesulphonate (DCCK) a radioimmunoassay was developed. This method involves use of an antibody against the dihydrolysergic acid moiety and an 125I-labelled dihydrolysergic tracer. The differentiation of dihydroergopeptides, lysergic acid and the ergopeptides was obtained by modification of extraction methods already published. The assay procedure detects around 10 pg/ml dihydroergotoxine. Dihydrolysergic acid and lysergic acid are not detectable up to about 6 ng/ml. Ergometrine and alpha-ergocryptine show cross-reactivities of 14% and 7.5%, respectively. All dihydroergopeptides included in dihydroergotoxine show the same cross-reactivity as dihydroergotoxine itself. Intra- and inter-assay variations were approximately 12% and 13%, respectively.
DMW - Deutsche Medizinische Wochenschrift
Arzneimittel-Forschung
8 patients with ventricular premature contractions were treated with prajmalium bitartrate (Neo-G... more 8 patients with ventricular premature contractions were treated with prajmalium bitartrate (Neo-Gilurytmal) 20 mg q.i.d. The electrocardiograms were continuously monitored by a computerized arrhythmia monitoring system. For definition of the drug's pharmacokinetic properties plasma concentrations were determined. 7 patients showed a marked arrhythmia reduction. Mean ventricular premature contraction frequency was significantly reduced 6 h after onset of treatment, maximum arrhythmia suppression to 34% of control was observed after 24 h of treatment. The correlation of antiarrhythmic response and plasma concentrations was good. Mean plasma concentrations during steady state conditions were 218 ng/ml. Plasma half-life was determined 7.3 h. The lower limit of therapeutic plasma concentrations was between 43 and 145 ng/ml. A mean total clearance of 344 ml/min indicates a low hepatic extraction of prajmalium bitartrate. Moreover, the distribution volume of 204 l suggests a high tissue affinity of the drug.
Arzneimittel-Forschung
Kidney independent glycosides offer a high measure of therapeutic safety in comparison with kidne... more Kidney independent glycosides offer a high measure of therapeutic safety in comparison with kidney dependent glycosides. The intoxication rate lies between 4 and 6%. The pharmacokinetic properties of pentaformylgitoxin (INN: gitoformate) are comparable with those for digitoxin. The active glycoside 16-formylgitoxin (INN: gitaloxin) is formed by rapid deformylation of the formyl residue on the sugar chain. The maintenance dose of 0.06 mg daily, based on the half-life, produces therapeutic concentrations in the range 6-30 ng/ml. The required loading dose, as for digitoxin, amounts to 10 times the maintenance dose.
DMW - Deutsche Medizinische Wochenschrift
ZFA. Zeitschrift für Allgemeinmedizin
International journal of clinical pharmacology, therapy, and toxicology
In a prospective randomized study 12 patients suffering from cirrhosis of the liver (stable phase... more In a prospective randomized study 12 patients suffering from cirrhosis of the liver (stable phase) and 12 healthy volunteers were treated daily with either 0.3 mg metildigoxin (Lanitop) or 0.4 mg beta-acetyldigoxin (Novodigal) orally. Every day the total serum digoxin concentrations of the patients and volunteers were measured by radioimmunoassay. Both digoxin and beta-methyldigoxin are measured by this method. In patients receiving metildigoxin therapy the ratio of beta-methyldigoxin/digoxin in the serum was determined by HPLC. The digoxin levels in patients with cirrhosis treated with metildigoxin were statistically significantly higher than in healthy volunteers. In patients with cirrhosis the proportion of serum beta-methyldigoxin averaged 77.7% of the total digoxin concentration, whereas the proportion was only 37.5% in healthy volunteers. With beta-acetyldigoxin there was no statistically significant difference between patients with cirrhosis and healthy volunteers. The higher total serum-digoxin levels in patients with cirrhosis of the liver after moderate saturation with metildigoxin are caused by reduced demethylation of beta-methyldigoxin to digoxin due to impaired liver function. A comparison with healthy volunteers showed that the reduced hepatic metabolism in the cirrhotic patients caused changes in the pharmacokinetics: a reduced metildigoxin clearance and a smaller distribution volume were found. According to our findings there is more danger of digitalis toxicity in patients with cirrhosis of the liver on a standard dosage of metildigoxin than on a standard dosage of beta-acetyldigoxin.
Arzneimittel-Forschung
The effect of beta-acetyldigoxin (Novodigal) on color vision in normal, healthy subjects was stud... more The effect of beta-acetyldigoxin (Novodigal) on color vision in normal, healthy subjects was studied using cortical evoked potentials. Initial results indicate a significant latency increase of one component of the visual evoked potential (VEP) and a dose dependency following a change of color from blue to red. The Farnsworth-Munsell-100-Hue test, however, showed no significant changes in color vision. It is postulated that the VEP is an even more sensitive measurement of color vision than subjective tests are.
International journal of clinical pharmacology, therapy, and toxicology
The relative bioavailability and plasma concentration profile of dihydroergotoxine as a solution,... more The relative bioavailability and plasma concentration profile of dihydroergotoxine as a solution, standard tablets and slow-release formulations have been compared in 12 healthy subjects following the application of 4-5 mg as a single dose or as 2-3 smaller dose units given at 5 h intervals. Plasma dihydroergotoxine concentrations were measured using a sensitive and highly specific radioimmunoassay procedure. The plasma concentration profile after a single 4.5 mg SR-capsule with relative bioavailability 92% (Oral solution, 4.5 mg as single dose = 100%), releasing 80% of the capsule contents within 8 h, was similar to that achieved following the application of 2-3 divided doses at 5 h intervals of a solution (relative bioavailability = 85%), standard tablet (relative bioavailability = 99%) or SR-tablets (relative bioavailability 78%). Slow-release formulations of dihydroergotoxine do not lead to high postdose concentrations as seen with solutions and standard tablets. Application of a single 4.5 mg SR-capsule can maintain prolonged plateau concentrations exceeding 100 pg/ml over 10 h. Reducing the rate of presentation of dihydroergotoxine to the body in the form of slow release formulations or by using spaced doses does not markedly affect bioavailability when compared to a solution.
International journal of clinical pharmacology and therapeutics
International journal of clinical pharmacology, therapy, and toxicology