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Biomedical subjects

A N Latham

Publications and source records attributed to A N Latham.

13 recordsLinked to original sources
PubMed1992

Influence of time of administration on verapamil pharmacokinetics.

The plasma concentration-time profile of verapamil was studied in eight healthy drug-free volunteers after oral administration of a single 80 mg dose of the drug on six separate occasions at different times of day (4 AM, 8 AM, noon, 4 PM, 8 PM, and midnight). The median maximum plasma concentration of verapamil was significantly higher after the 8 AM and noon administrations (p less than 0.05) than at any other time. The median area under the concentration-time curve was also significantly higher (p less than 0.05) after administration at 8 AM and noon than at other times. The median time to maximum concentration was not significantly different at any time point (p greater than 0.05). It is possible that concentration-related adverse effects of verapamil could be avoided by choosing the time of day when the drug is prescribed. This concept may also apply to other drugs that have circadian effects in their pharmacokinetic profiles.

Administration, Oral↗
PubMed1989

The efficacy and duration of action of sustained-release verapamil in essential hypertension.

The blood-pressure (BP)-lowering efficacy of sustained-release verapamil, using both clinic and ambulatory measurements, was assessed in patients with essential hypertension. In study 1, a between-patient comparison, we compared verapamil (n = 12) with propranolol (n = 10). Dosage of each agent was titrated to achieve optimal clinic BP control and this dose was maintained for the duration of the study. Both agents lowered clinic systolic and diastolic BP. Mean daily ambulatory BP was also reduced with propranolol by 23/8 mm Hg and with verapamil by 13/8 mm Hg. The mean percentage reduction of systolic BP was significantly greater with propranolol (p less than 0.01). In study 2 we assessed the duration of action of sustained-release verapamil (240 mg once daily) in 14 patients. Both clinic and mean ambulatory BP were significantly reduced by 17/12 and 16/8 mm Hg, respectively, and this reduction was maintained throughout the day. We conclude that this formulation of sustained-release verapamil is effective in lowering blood pressure in mild-to-moderate hypertension and that once-daily dosage with 240 mg maintains ambulatory BP reduction throughout the dosing interval.

Adult↗
PubMed1989

The effects of verapamil and propranolol on quality of life in hypertension.

Quality of life was evaluated in a four-month randomised double-blind trial of verapamil compared with propranolol in the treatment of hypertension in 94 patients in the UK. Scores on a health status index, measuring activity and perceived health, increased in verapamil patients compared to a decrease in propranolol patients (P = 0.01). Measures of psychiatric morbidity also tended to improve with verapamil and deteriorate with propranolol. Propranolol patients reported more symptoms overall compared with verapamil (P less than 0.05). The prevalence of certain symptoms--headaches, weak limbs and slower walking pace, increased significantly with propranolol compared with verapamil, but constipation was more common in verapamil patients (P less than 0.05). After four months, diastolic blood pressure averaged 86.2 mmHg with verapamil and 90.3 mmHg with propranolol (P = 0.02). However, this difference in final blood pressure did not explain the more favourable quality of life scores with verapamil, and the data suggest that health-related well-being is higher with this drug.

Adult↗
PubMed1988

Verapamil SR and propranolol LA: a comparison of efficacy and side effects in the treatment of mild to moderate hypertension.

The efficacy, safety and toleration of sustained release verapamil (Securon SR, Knoll) and long acting propranolol (Inderal LA, ICI) in the treatment of mild to moderate hypertension were compared in a randomized, double-blind, parallel group study. Both drugs were of similar efficacy and were well tolerated in the majority of patients. However, in the verapamil SR treated group side-effects resulted in significantly fewer drug-related withdrawals.

Adult↗
PubMed1977

Simultaneous determination of anticonvulsant drugs by gas-liquid chromatography.

A quantitative gas-liquid chromatographic method for the determination of blood levels of ethosuximide, phenobarbitone, primidone and diphenylhydantoin is described. All four compounds are determined using 1 ml of serum. A simple, direct extraction technique is employed. Ethosuximide is analysed without derivatization. Subsequent flash alkylation with trimethylanilinium hydroxide allows the simultaneous determination of phenobarbitone, primidone, and diphenylhydantoin.

Anticonvulsants↗
PubMed1977

A new chronically cannulated carotid artery preparation for determination of drug half-lives in quinea pig.

A reliable procedure for implanting a cannula into the carotid artery of the guinea pig is described. The gaseous anaesthetic used provided excellent control, rapid recovery, and caused no fatalities. There was no evidence of postoperative infection and patency of the cannula could be maintained for 21 days after surgery. There was no indication of postoperative trauma and removal of blood appeared to be painless. Efficacy of the preparation was demonstrated by repeated removal of 3-ml volumes of blood for the determination of the half-life of phenobarbital acutely in five animals and chronically in three guinea pigs treated with the drug for 14 days. Administration of phenobarbital twice daily (20 or 50 mg/kg, ip) for 1 week increased its clearance rate fivefold. Treatment for an additional week produced a further increase in phenobarbital clearance. The cannulated guinea pig preparation described should allow determination of the pharmacokinetics of many drugs in this species.

Animals↗
PubMed1976

Simultaneous quantitative gas-chromatographic analysis of ethosuximide, phenobarbitone, primidone and diphenylhydantoin.

1 Therapeutic serum concentrations of ethosuximide, phenobarbitone, primidone, and dipheylhydantoin were assayed from 1 ml of human serum. The extraction procedure was common to all four drugs and three internal standards. 2 Subsequent isothermal gas chromatographic analysis of serum extracts produced well resolved peaks for the underivatized quantitation of ethosuximide and phenobarbitone. Primidone and diphenylhydantoin were determined as methylated derivatives. 3 Mean coefficients of variation for the assay of each drug were less 7% on a newly packed and conditioned column and less than 10% after the technique had been in continuous use for 3 months. 4 The advantage of quantitation relative to peak area ratios rather than peak height ratios was minimal for the determination of ethosuximide, primidone and diphenylhydantoin but appeared significant for the assay of phenobarbitone.

Chromatography, Gas↗
PubMed1976

Phenobarbitone-induced urinary excretions of D-glucaric acid and 6beta-hydroxycortisol in man.

The urinary excretion of D-glucaric acid and 6beta-hydroxycortisol were determined in normal subjects before, during, and after 14 days treatment with placebo or phenobarbitone. The excretion of both metabolites was significantly potentiated by phenobarbitone and returned to baseline values 1 month after treatment was withdrawn. It was suggested that the determination of urinary D-glucaric acid reflects the activity of the hepatic microsomal mixed function oxidase system after the administration of an inducing agent such as phenobarbitone.

Adult↗
PubMed1976

Binding of anticonvulsant drugs to cytochrome P-450: correlation with evidence of induction of hepatic microsomal enzymes.

Mephenytoin, diphenylhydantoin, pheneturide, and phenobarbital produced a concentration-dependent inhibition in the binding of hexobarbital to cytochrome P-450 at the type 1 site, while sulthiame slightly potentiated, and ethosuximide did not affect the binding characteristic of hexobarbital. Diphenylhydantoin, phenobarbital, and pheneturide have previously been shown to enhance the urinary excretion of D-glucaric acid (DGA), while sulthiame inhibited the potentiation of DGA excretion caused by these drugs, and ethosuximide produced no change. The results suggest a close relationship between the ability of these drugs to induce hepatic microsomal drug-metabolizing enzyme systems (as indicated by enhancement of DGA excretion) and binding behaviour at the type 1 site.

Animals↗