Pharmacokinetics and biotransformation of the new benzodiazepine, lormetazepam, in man
- 44 Downloads
The concentrations of lormetazepam and its glucuronide in plasma and milk were determined during administration of 10 daily doses of lormetazepam 2 mg (2 tablets of NOCTAMID® - 1) to five mothers delivered by Caesarian section. Their babies were breast-fed throughout the study, and the plasma levels of lormetazepam and its glucuronide were determined three times in the babies. At 12 and 24h after administration, the plasma level of lormetazepam was about 3.5 ng/ml and 1.8 ng/ml in mothers, and below 0.09 ng/ml in the children. In milk the lormetazepam concentration was below 0.2 ng/ml. The plasma level of glucuronide varied between 24 ng/ml at 12h and 11 ng/ml 24h after administration. Almost no accumulation of unchanged lormetazepam was observed (factor: 1.3). The ratio of the levels of lormetazepam in milk and plasma was estimated to be below 0.06, and for the glucuronide the ratio was 0.04. The quantity of free and conjugated active ingredient transferred to the children via breast milk was calculated to be at most 100 ng/kg, corresponding to 0.35% of the maternal dose, which is regarded as tolerable.
Key wordsbenzodiazepine lormetazepam lormetazepam glucuronide transfer to milk pharmacokinetics
Unable to display preview. Download preview PDF.
- 1.Oswald I, Adam K, Burrow S, Idzikowski C (1979) The effects of two hypnotics on sleep; subjective feelings and skilled performance. In: Passouant P, Oswald I (eds) Pharmacology in the state of alertness, Pergamon Press, Oxford, pp 51–63Google Scholar
- 2.Heidrich H, Ott H, Beach RC (1981) Lormetazepam — a benzodiazepine derivative without hangover effect? A double-blind study in a general practice setting. Int J Clin Pharmacol Ther Toxicol 19: 11–19Google Scholar
- 3.Sastre YH, Hentschel H-J, Fichte K (1981) Comparative efficacy of lormetazepam (Noctamid®) and diazepam (Valium®) in 100 out-patients with insomnia. J Int Med Res 9: 199–202Google Scholar
- 4.Girkin R, Baldock GA, Chasseaud LF, Hümpel M, Hawkins DR, Mayo BS (1980) The absorption, distribution and excretion of 14C-lormetazepam in dogs, rabbits, rats and rhesus monkeys. Xenobiotica 10: 401–411Google Scholar
- 5.Mayo BS, Hawkins DR, Hümpel M, Chasseaud LF, Baldock GA, Girkin R (1980) The biotransformation of 14C-lormetazepam in dogs, rabbits and rhesus monkeys. Xenobiotica 10: 413–420Google Scholar
- 6.Hümpel M, Illi V, Milius W, Wendt H, Kurowski M (1979) The pharmacokinetics and biotransformation of a new benzodiazepine (lormetazepam) in humans. I. Absorption, distribution, elimination and metabolism of lormetazepam-5-14C. Eur J Drug Metabol Pharmacokinet 4: 237–243Google Scholar
- 7.Hümpel M, Nieuweboer B, Milius W, Hanke H, Wendt H (1980) Kinetics and biotransformation of lormetazepam. II. Radioimmunologic determinations in plasma and urine of young and elderly subjects: first-pass-effect. Clin Pharmacol Ther 28: 673–679Google Scholar
- 8.Erkkola R, Kanto J (1972) Diazepam and breast feeding. Lancet 1: 1235–1236Google Scholar
- 9.Brandt R (1976) Passage of diazepam and desmethyldiazepam into breast milk. Arzneim.-Forsch (Drug Res) 26: 454–457Google Scholar
- 10.Kanto J, Aaltonen L, Kangas L (1979) Placental transfer and breast milk levels of flunitrazepam. Curr Ther Res 26: 539–546Google Scholar
- 11.Cole AP, Hailey DM (1975) Diazepam and active metabolite in breast milk and their transfer to the neonate. Arch Dis Child 50: 741–742Google Scholar