Pharmacokinetics of midazolam used as an intravenous induction agent for patients over 80 years of age.

The pharmacokinetic profile of 0.2 mg kg-1 midazolam given i.v., for induction of anaesthesia, was compared in young subjects and in those who were over 80 years of age. Thirty-five patients were allocated into four groups according to their sex and age. Plasma samples were drawn before midazolam injection and at regular intervals over 24 h following injection. Plasma midazolam concentrations were measured by electron capture gas-liquid chromatography. Equilibrium dialysis was used to assess the plasma protein binding of midazolam. Distribution volume (Vdss) was significantly increased in elderly subjects when compared to young subjects of the same sex (young vs. elderly males, Vdss = 1.22 +/- 0.31 l kg-1 and 2.47 +/- 0.98 l kg-1 respectively; and young vs. elderly females, Vdss = 0.91 +/- 0.29 l kg-1 and 1.70 +/- 0.78 l kg-1 respectively). Total body clearance was significantly reduced in elderly males compared with young males (5.60 +/- 1.77 ml min-1 kg-1 vs. 8.10 +/- 3.58 ml min-1 kg-1). No significant difference in clearance was found between young and elderly females (6.08 +/- 2.04 ml min-1 kg-1 vs. 9.14 +/- 3.36 ml min-1 kg-1). As a consequence, elimination half-life (T1/2E) was significantly prolonged in elderly compared to young males (8.52 +/- 5.4 h vs. 2.77 +/- 0.80 h). In contrast, T1/2E was unchanged in elderly compared to young females (2.99 +/- 0.86 h vs. 2.86 +/- 1.04 h). Midazolam plasma protein binding was not influenced by age and sex.

[Immunological assay of sisomycin by fluorescence polarization]. / Dosage immunologique de la sisomicine, par polarisation de fluorescence.

Fluorescence polarization immunoassays (FPIA) of aminoglycoside antibiotics (gentamicin, tobramycin and amikacin) in plasma have been described. The use of sisomicin, a structural analogue of a C1a gentamicin fraction, is an alternative to gentamicin therapy for economical reasons. We have tested a therapeutic monitoring of this drug bases on FPIA using its croos reaction with gentamicin. Tracer (gentamicin labelled with fluorescein) and antisera were purchased from Abbott S.A. (gentamicin kit). Standard curves were obtained with sisomicin standard plasma samples. Within run and run-to-run precisions expressed as coefficient of variation were lower than 9.2 p. cent. The measurement of concentrations as low as 0.15 mg/l are possible. In order to evaluate specificity of this assay in clinical situation, we compared FPIA and liquid chromatography results.

Quantitative liquid chromatography of allopurinol and oxypurinol in human plasma and urine.

A high performance liquid chromatographic (HPLC) assay is described for allopurinol and oxypurinol determination in human plasma and urine, in the range expected during therapy. The procedure involves addition of trichloroacetic acid to samples, followed by centrifugation. The supernatant is then neutralized and analyzed by reversed-phase HPLC. Characteristics of the method are reported, and data are presented on its application to the pharmacokinetics studies. Separation is optimal with an octadecylsilane (ODS) stationary phase and a sodium acetate mobile phase adjusted to pH 7.2 for plasma and pH 5 for urine.