Disposition of intravenous diazepam in young men and women

Hg, Giles; Sellers, Edward M.; Naranjo, Claudio A.; Rc, Frecker; Dj, Greenblatt

doi:10.1007/bf00544599

Cited by 21 publications

(10 citation statements)

References 26 publications

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“…In each case the extent of protein binding was lower in women than in men of comparable age. Giles et al (1981), Ochs et a1. (1981) and Wood and Wood (1981), however, observed no significant sex-related differences in the extent of plasma protein binding of diazepam.…”

Section: Protein Bindingmentioning

confidence: 96%

Sex-Related Differences in Drug Disposition in Man

Wilson¹

1984

Clinical Pharmacokinetics

154

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Sex-related differences in the disposition of some analgesics, anxiolytics and hypnotics have recently been reported. With certain benzodiazepines, sex has been shown to be a more important determinant of variability in drug disposition than age, while with other benzodiazepines an age-related decline in clearance was more pronounced in men than women. In young healthy adults these sex-related differences in drug disposition were related to the phase of the menstrual cycle, oral contraceptive steroid administration, and variations in plasma concentrations of albumin, alpha 1-acid glycoprotein, free fatty acids and sex hormones. While none of the sex-related differences so far reported necessitates the modification of a therapeutic dosage regimen, it is prudent that future protocols for pharmacokinetic studies should regard age, sex, the menstrual cycle and oral contraceptive steroids as potential sources of variability.

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Section: Protein Bindingmentioning

confidence: 96%

Sex-Related Differences in Drug Disposition in Man

Wilson¹

1984

Clinical Pharmacokinetics

154

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“…Distribution of brotizolam proceeded quite rapidly and elimination was quite fast with elimination half-lives between 3 and 6 h. The volume of distribution was about 401 (0.66 1/kg), which is approximately the volume of total body water. This is small as compared to other diazepines: the benzodiazepines diazepam and nitrazepam have volumes of distribution of about 1.1-1.5 1/kg (Giles et al, 1981;Greenblatt et al, 1980) and 2 1/kg (Jochemsen et al., 1982a) respectively; the 3- hydroxy-benzodiazepines lorazepam and temazepam have volumes of distribution of about 1.3 1/kg (Greenblatt et al, 1979;Divoll et al, 1981;Jochemsen et al, unpublished results) and the short-acting benzodiazepines triazolam (triazolo-derivative) and (Jochemsen et al, 1983) and 1.7 1/kg respectively. The total clearance of brotizolam was 113 ml/min, indicating that drug elimination is predominantly dependent on drug metabolizing enzyme activity and not on hepatic drug blood flow (low extraction drug).…”

Section: Discussionmentioning

confidence: 87%

“…Distribution of brotizolam proceeded quite rapidly and elimination was quite fast with elimination half-lives between 3 and 6 h. The volume of distribution was about 401 (0.66 1/kg), which is approximately the volume of total body water. This is small as compared to other diazepines: the benzodiazepines diazepam and nitrazepam have volumes of distribution of about 1.1-1.5 1/kg (Giles et al, 1981;Greenblatt et al, 1980) and 2 1/kg (Jochemsen et al., 1982a) respectively; the 3- (Jochemsen et al, 1983) and 1.7 1/kg method which is relatively independent of changes in clearance (Collier & Reigelman, 1981). By this method (equation (7)), the same results were obtained as with the traditional method (equation (6)) ( Table 4), indicating that the intra-individual differences in half-life were indeed due to changes in clearance.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of brotizolam in healthy subjects following intravenous and oral administration.

Jochemsen¹,

Jg²,

Hermans³

et al. 1983

Brit J Clinical Pharma

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Pharmacokinetics and bioavailability of brotizolam after i.v. and oral administration were studied in healthy young volunteers. Kinetic parameters after i.v. administration were: volume of distribution 0.66 +/‐ 0.19 1/kg, total plasma clearance 113 +/‐ 28 ml/min, distribution half‐life 11 +/‐ 6 min, and elimination half‐life 4.8 +/‐ 1.4 h (mean values +/‐ s.d.). Kinetic parameters after oral administration were: absorption lag‐time 8 +/‐ 12 min, absorption half‐life 10 +/‐ 11 min, and elimination half‐life 5.1 +/‐ 1.2 h (mean values +/‐ s.d.). Bioavailability of brotizolam was 70 +/‐ 22% when calculated by comparing oral and intravenous area‐under‐curve values, corrected for intra‐individual half‐life differences. An alternative calculation method, which is relatively independent of large clearance variations, provided a bioavailability of 70 +/‐ 24% (range: 47‐117%).

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“…Entin, les contraceptifs oraux sont aI'origine de frequentes interactions medicamenteuses, comme avec le diazepam et le chlordiazepam, pour lesquels (comme dans le cas de toutes les benzodiazepines metabolisees par oxydation) ils reduisent la clairance (35,36). Le mecanisme d'action serait ici aussi l'inhibition enzymatique (cytochrome P 450IIIA) (12).…”

Section: Hypnotiques Sedatifs Et Anxiolytiquesunclassified

Des variations intersexuelles relatives aux traitements en psychiatrie

Godfroid¹

1999

Can J Psychiatry

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Disposition of intravenous diazepam in young men and women

Cited by 21 publications

References 26 publications

Sex-Related Differences in Drug Disposition in Man

Sex-Related Differences in Drug Disposition in Man

Pharmacokinetics of brotizolam in healthy subjects following intravenous and oral administration.

Des variations intersexuelles relatives aux traitements en psychiatrie

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