Bromazepam pharmacokinetics: Influence of age, gender, oral contraceptives, cimetidine, and propranolol

  title={Bromazepam pharmacokinetics: Influence of age, gender, oral contraceptives, cimetidine, and propranolol},
  author={Hermann R. Ochs and David J Greenblatt and Hylar L Friedman and Ethan S. Burstein and Ann Locniskar and Jerold S. Harmatz and RichardI. Shader},
  journal={Clinical Pharmacology \& Therapeutics},
Pharmacokinetics of the benzodiazepine bromazepam were evaluated in volunteer subjects who received single 6 mg oral doses followed by blood sampling during the next 48 hours. Age and gender effects were studied in 32 subjects, divided into young (aged 21 to 29 years) and elderly (aged 60 to 81 years) groups. Compared with young subjects, the elderly had significantly higher peak serum bromazepam concentrations (132 vs. 82 ng/ml), smaller volume of distribution (0.88 vs. 1.44 L/kg), lower oral… 

Zolpidem Pharmacokinetic Properties in Young Females: Influence of Smoking and Oral Contraceptive Use

Differences in zolpidem kinetics associated with smoking may be explained by the small contribution of cytochrome P450‐1A2 to net clearance of zolPidem, which is quantitatively small and not likely to be ofclinical importance.

Alprazolam Pharmacokinetics in Women on Low‐Dose Oral Contraceptives

Alprazolam free fraction in plasma was slightly but significantly greater in the oral contraceptive group as opposed to the control group, however, comparison of free clearance between groups revealed no significant difference.

Doxylamine and Diphenhydramine Pharmacokinetics in Women on Low‐Dose Estrogen Oral Contraceptives

Low‐dose estrogen‐containing oral contraceptives do not significantly influence the pharmacokinetics of the antihistamines doxylamine or diphenhydramine, and these differences were statistically significant.

Pharmacokinetics of quinine in young and elderly subjects.

Influence of Oral Contraceptive Use and Cigarette Smoking, Alone and Together, on Antipyrine Pharmacokinetics

The opposing effects on antipyrine clearance of the induction of metabolism by cigarette smoking and the inhibition due to low dose oral contraceptive use in effect negate each other when combined in humans.

Comparative kinetics and response to the benzodiazepine agonists triazolam and zolpidem: evaluation of sex-dependent differences.

The complete dependence of triazolam clearance on CYP3A activity, as opposed to the mixed CYP participation in zolpidem clearance, may explain the differing sex effects on clearance of the two compounds.

A comparative pharmacokinetic and dynamic evaluation of alprazolam sustained-release, bromazepam, and lorazepam.

Alprazolam SR sustained that concentration better than did the other two formulations, but not bromazepam, and produced significantly more sedation than placebo.

The effect of itraconazole on the pharmacokinetics and pharmacodynamics of bromazepam in healthy volunteers

The pharmacokinetics and pharmacodynamics of bromazepam were not affected by itraconazole, suggesting that CYP3A4 is not involved in the metabolism of bruzepam to a major extent.

The influence of age and gender on the stereoselective metabolism and pharmacokinetics of mephobarbital in humans

In this clinical investigation, four groups of subjects (eight young women and eight young men [age range, 18 to 25 years], and eight elderly women and eight elderly men [>60 years of age]) received

Effect of Fluconazole on the Pharmacokinetics and Pharmacodynamics of Oral and Rectal Bromazepam: An Application of Electroencephalography as the Pharmacodynamic Method

The EEG method provided pharmacodynamic data that clearly reflected the pharmacokinetics of bromazepam and fluconazole and may be due to avoidance of degradation occurring in the gastrointestinal tract.



Age, sex, and nitrazepam kinetics: Relation to antipyrine disposition

Age minimally influences nitrazepam clearance (accomplished mainly by nitroreduction), which in turn is not significantly related to antipyrine oxidizing capacity.

Lorazepam and oxazepam kinetics in women on low‐dose oral contraceptives

Women on low‐dose estrogen oral contraceptives (OC) and drug‐free control women matched for age, weight, and cigarette smoking habits, received single 2‐mg IV doses of lorazepam or single 30‐mg oral doses of oxazepams, two benzodiazepines metabolized by glucuronide conjugation, finding metabolic clearance by glucuridation is not significantly affected by OC.

Cimetidine Impairs Clearance of Antipyrine and Desmethyldiazepam in the Elderly

Cimetidine prolonged desmethyldiazepam half‐life similarly in young and elderly groups and similarly reduced metabolic clearance and the elderly population may already have an impaired capacity to oxidize drugs, which is further impaired by coadministration of cimetidine.

Differential effects of isoniazid and oral contraceptive steroids on antipyrine oxidation and acetaminophen conjugation.

The capacities for drug oxidation and conjugation appear to be controlled by different mechanisms, and clearance of antipyrine and acetaminophen across both studies was not statistically significantly correlated within individuals.

Kinetics of diazepam, midazolam, and lorazepam in cigarette smokers.

There was no significant difference in mean clearance of diazepam, midazolam, or lorazepam in non-smoking vs smoking subjects, and differences in pharmacokinetics are unlikely to account for altered sensitivity to benzodiazepines that may occur in cigarette smokers.

Single- and multiple-dose pharmacokinetics of oral alprazolam in healthy smoking and nonsmoking men.

Steady-state pharmacokinetic values during the multiple-dose phase correlated with values observed following the single dose, and alprazolam elimination was more rapid in smokers than in nonsmokers.

Propranolol interactions with diazepam, lorazepam, and alprazolam.

Propranolol induces a small but significant reduction in clearance of diazepam, biotransformed mainly by the oxidative reaction of N-demethylation, and does not impair lorazepam clearance by glucuronide conjugation nor that of alprazolam by aliphatic hydroxylation.

Differential Effects of Oral Contraceptive Steroids on the Metabolism of Benzodiazepines

It is concluded that OCS exert a differential effect on the elimination of benzodiazepines, whereby oxidation of chlordiazepoxide is impaired while the glucuronidation of lorazepam and oxzepam is enhanced by OCS.

Interaction of Cimetidine with Oxazepam, Lorazepam, and Flurazepam

Cimetidine has little or no influence on the absorption or disposition of oxazepam and lorazep am, two benzodiazepines biotransformed by glucuronide conjugation, however, Cimetidine slows the elimination of flurazepham's metabolite, desalkylflurazEPam, which is biotranformed by oxidation.

Impairment of Antipyrine Clearance in Humans by Propranolol

Propranolol prolongs the half-life and reduces the clearance or biotransformation rate of antipyrine, a drug whose clearance is independent of hepatic blood flow, and may influence the activity of hepatitis microsomal enzymes responsible for drug hydroxylation.