PubMed Health⌕ Search

Biomedical subjects

M M Rees

Publications and source records attributed to M M Rees.

4 recordsLinked to original sources
PubMed1985

Dose dependent pharmacokinetics of midazolam.

The pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were investigated following oral administration of 7.5, 15 and 30 mg doses of midazolam in solution to 12 healthy subjects. Compared to the 7.5 mg dose, the Cmax and AUC parameters of both midazolam and 1-hydroxymethylmidazolam increased proportionally after the 15 mg dose and more than proportionally after the 30 mg dose. The t1/2 for midazolam remained relatively constant between the 7.5 and 15 mg doses whereas it increased slightly but significantly after the 30 mg dose. These data indicated that the pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were linear between the 7.5 and 15 mg oral dose range. However, after the 30 mg dose, the systemic availability of midazolam and the AUC for 1-hydroxymethylmidazolam appeared to be greater than that anticipated from the lower doses, possibly due to saturation of midazolam first-pass metabolism. This is not expected to have any clinical significance under the conditions of therapeutic use.

Adult↗
PubMed1984

Age and cibenzoline disposition.

Oral cibenzoline kinetics were followed in 36 healthy subjects aged from 22 to 78 yr divided into groups of six subjects per decade between 20 and 80 yr. Each received a single, oral, 160-mg dose of cibenzoline. Blood and urine samples were collected for 72 hr. Cibenzoline plasma and urine concentrations were measured by HPLC. Maximum plasma cibenzoline concentrations (Cmax) ranged from 283 to 1100 ng/ml and occurred 1 to 2.5 hr after dosing. Apparent oral clearance (ClT) ranged from 401 to 1677 ml/min and the t 1/2 ranged from 5.9 to 13.4 hr. Nonrenal clearance (ClNR) ranged from 65 to 1113 ml/min, renal clearance (ClR) ranged from 165 to 645 ml/min, and 31% to 86% of the dose was recovered unchanged in urine (Xu). The volume of distribution (Vd) was large, ranging from 236 to 948 l. There was a significant relationship between age and the following kinetic parameters: Cmax, Xu, t 1/2 (all of which increased with age), ClT, ClR, ClNR, the terminal elimination rate constant beta, and Vd (which decreased with age). Mean ClT was 999 +/- 371 ml/min in the 20- to 30-yr age group and was 465 +/- 78 ml/min in the 70- to 80-yr age group. The change in ClT with age resulted from a decreased in both ClR and ClNR. Mean t 1/2 varied from 7 hr in the youngest group to 10.5 hr in the oldest group. The age-related changes in cibenzoline kinetics occurred over the entire age range studied and the relationship between age and these kinetic parameters appeared to be linear.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗