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Biomedical subjects

R Jochemsen

Publications and source records attributed to R Jochemsen.

44 records · Page 3Linked to original sources
PubMed1982

Influence of sex, menstrual cycle and oral contraception on the disposition of nitrazepam.

1 The effects of sex and oral contraceptives (OC) on the disposition of oral nitrazepam were studied in six healthy young males, in six healthy young females in the follicular and luteal phase of the menstrual cycle and in six healthy young females using OC-steroids in two stages of the pill cycle. 2 There was no influence of the menstrual cycle on the pharmacokinetic parameters of nitrazepam, nor was there a significant difference between these parameters in males and females in either phase of the cycle. The elimination half-life was 27.3 +/- 1.3 h in males, 27.7 +/- 1.5 h in females in the follicular phase and 29.6 +/- 1.4 h in the luteal phase of the menstrual cycle. Total plasma clearance was 59.3 +/- 2.7 ml/min, 58.2 +/- 3.3 and 55.8 +/- 5.0 ml/min respectively. 3 The use of OC-steroids did not significantly alter the elimination half-life of nitrazepam: 30.6 +/- 2.3 and 31.2 +/- 2.2 h in the first and second half of the pill cycle. The total nitrazepam clearance in these females (46.6 +/- 4.6 and 45.6 +/- 4.1 ml/min) was significantly lower than in males (P less than 0.05). 4 The protein unbound fraction of nitrazepam was progressively higher going from males (11.4 +/- 0.1%) to females in the luteal phase of the cycle (12.4 +/- 0.5%) to females using OC-steroids (13.5 +/- 0.4%). Only the difference between males and females using OC-steroids was statistically significant. 5 The clearance calculated relative to the unbound drug (intrinsic clearance) was significantly decreased in females taking OC-steroids as compared to males and females not taking them (Cli = 323 +/- 30 ml/min in females using OC-steroids, 530 +/- 37 ml/min in males and 459 +/- 40 ml/min in females). 6 The results of this study are not likely to have important consequences for dosage of nitrazepam as an hypnotic. The most pronounced effect observed was inhibition of nitrazepam clearance and especially intrinsic clearance by OC-steroids. Females on OC-steroids taking a nitrazepam tablet every evening, will have highly steady levels of nitrazepam (and certainly of unbound nitrazepam) than males or females not taking OC-steroids.

Adult↗
PubMed1980

Pharmacokinetics of benzodiazepines. Short-acting versus long-acting.

Among the various benzodiazepines large differences exist with regard to their pharmacokinetic properties and metabolism in man. Some are eliminated from the body at a relatively slow rate (e. g. diazepam), others are metabolized rather rapidly (e. g. oxazepam, temazepam, triazolam). Several benzodiazepines have the long-acting metabolite N-desmethyldiazepam in common (diazepam, fosazepam, prazepam, clorazepate). Such differences may be very important clinically because pharmacokinetic factors will determine the duration of drug effect and pharmacokinetic parameters constitute the basis for a rational dosage regimen. For the various clinical indications of benzodiazepines the required duration of drug action differs quite fundamentally. In anticonvulsant and anti-anxiety treatment continuous treatment is pursued, so that compounds with long elimination half-lives of parent drug or active metabolites are of advantage. If on the other hand a benzodiazepine is taken as a hypnotic, the duration of action should be restricted to the night, hence a compound with a short elimination half-life is to be preferred. A review is given of the pharmacokinetics of the major benzodiazepines presently available.

Anti-Anxiety Agents↗
PubMedDate not supplied

Comparative pharmacokinetics of midazolam and loprazolam in healthy subjects after oral administration.

The pharmacokinetics of oral midazolam (Dormicum, 15 mg) and loprazolam (Dormonoct, 1 mg) were studied in eight healthy young volunteers in a cross-over design. Plasma concentrations of midazolam were measured with a gas chromatographic method and loprazolam concentrations were determined by a radio-receptor technique. Absorption of midazolam proceeded very rapidly (median tmax = 0.4 h) and a rapid onset of sedative action was observed. Loprazolam absorption was relatively slow (median tmax = 3 h) and its absorption profile was often irregular. Most subjects fell asleep before peak concentrations were reached. Median peak concentrations were 94 ng ml-1 and 3.1 ng ml-1 for midazolam and loprozolam, respectively. The median elimination half-life of midazolam was 1.8 h and that of loprazolam 15 h. It is possible that the elimination half-life of loprazolam as determined by radioreceptor assay is determined by active metabolites rather than by loprazolam itself. Midazolam elimination half-life was the same when determined by radioreceptor assay or by GLC. There was no significant correlation between the half-lives of the two drugs.

Administration, Oral↗
PubMedDate not supplied

Pharmacokinetics of sustained and immediate release formulations of indapamide after single and repeated oral administration in healthy volunteers.

The pharmacokinetics of a 2.5 mg immediate release (IR) formulation of indapamide was compared to a 1.5 mg sustained release (SR) formulation of indapamide after single and repeated oral administration dose using double blind randomised cross-over studies. In the first study, 12 subjects received a single dose of each treatment: IR fasted, SR fasted or with food. In the second study one tablet of either formulation was administered daily for one week at breakfast. In each study, blood samples were collected pre dose (Cmin) and up to 120 h after the last dose. Urine was collected over the dosing interval (24 h). Following a single oral administration the SR formulation had a lower dose-normalised Cmax compared to the IR formulation (17.6 +/- 6.3 vs. 39.3 +/- 11.0 ng x mL(-1), respectively), a much longer t(max) (12.3 +/- 0.4 vs. 0.8 +/- 0.3 h) and a greater t75 (15.3 +/- 6.1 vs. 1.8 +/- 1.4 h) but there were no differences in dose-normalised AUC (559 +/- 125 and 564 +/- 146 ng x h x mL(-1)) nor in t(1/2z) values (14.8 +/- 2.8 vs. 18.4 +/- 13.4 h). The SR formulation clearly demonstrated sustained release characteristics as compared to the IR formulation. Food co-administration had no effect on dose-normalised AUC for the SR formulation. After repeated administration, steady-state was achieved by day 5. The absorption rate of the SR formulation was lower and the 24 h peak-to-trough fluctuation was 4-fold lower compared to the IR formulation. After dose correction there wasno change in AUC, (726 +/- 207 and 690 +/- 183 ng x mL(-1) x h for SR and IR, respectively). The elimination parameters (t(1,2z), Ae(tau), and CLr) remained unchanged. The SR formulation showed sustained release of indapamide with a reduction in peak concentration, while steady-state level was not affected by formulations. The two formulations have the same bioavailability.

Administration, Oral↗