caa a22 4500 465812392 CHVBK 20180323112120.0 cr unu---uuuuu 170327e19901001xx s 000 0 eng 10.1007/BF03190221 doi (NATIONALLICENCE)springer-10.1007/BF03190221 Pharmacokinetics and tolerance of romazarit after oral administration of ascending single doses to healthy human volunteers [Elektronische Daten] [P. Williams, G. Muirhead, E. Worth, R. Zimmer, P. Lücker] Summary: Forty-four healthy male volunteers participated in an investigation of the pharmacokinetics and tolerance of single oral doses of romazarit, a potential disease-modifying antirheumatic drug. The study design involved single oral doses in ascending sequence from 40 to 1500 mg. At each dosage 9 volunteers were studied, of whom 6 received romazarit and 3 received placebo capsules in a double-blind manner. Tolerance was assessed before and after each of the 57 romazarit and 27 placebo doses. Plasma and urinary concentrations of romazarit were measured by HPLC with UV detection. Model-independent pharmacokinetic analyses showed that romazarit was rapidly and extensively absorbed in a dose-proportional manner. Urinary recovery of drug related material was about 70% of the dose and almost all in the form of labile metabolites (probably acyl glucuronides). Clearance was faster (>3 1/h) at doses below 700 mg, than in the range 700-1500 mg (1.7 1/h). It is suggested that two or more clearance mechanisms are present. One of these mechanisms is saturable and may involve a reversible ester glucuronide formation coupled with saturable tubular secretion of glucuronides. Romazarit was well tolerated in these healthy volunteers. There were two reports of stomach pain, one associated with vomiting. Changes in laboratory safety test results and in measurements of vital signs were similar in frequency and magnitude after romazarit and after placebo doses. Springer-Verlag, 1990 Romazarit nationallicence Pharmacokinetics nationallicence dose proportionality nationallicence non-linearity nationallicence Williams P. Pharmacokinetics & Metabolism Department, Roche Products Ltd, PO Box 8, AL7 3AY, Welwyn Garden City, Herts, UK aut Muirhead G. Pharmacokinetics & Metabolism Department, Roche Products Ltd, PO Box 8, AL7 3AY, Welwyn Garden City, Herts, UK aut Worth E. Pharmacokinetics & Metabolism Department, Roche Products Ltd, PO Box 8, AL7 3AY, Welwyn Garden City, Herts, UK aut Zimmer R. Department PKF/PD, F Hoffmann-La Roche Ltd, Basle, Switzerland aut Lücker P. Institut für Klinische Pharmakologie, Bobenheim, Grunstadt, FRG aut European Journal of Drug Metabolism and Pharmacokinetics Springer-Verlag 15/4(1990-10-01), 317-322 0378-7966 15:4<317 1990 15 13318 https://doi.org/10.1007/BF03190221 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF03190221 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Williams P. Pharmacokinetics & Metabolism Department, Roche Products Ltd, PO Box 8, AL7 3AY, Welwyn Garden City, Herts, UK aut NATIONALLICENCE 700 1- Muirhead G. Pharmacokinetics & Metabolism Department, Roche Products Ltd, PO Box 8, AL7 3AY, Welwyn Garden City, Herts, UK aut NATIONALLICENCE 700 1- Worth E. Pharmacokinetics & Metabolism Department, Roche Products Ltd, PO Box 8, AL7 3AY, Welwyn Garden City, Herts, UK aut NATIONALLICENCE 700 1- Zimmer R. Department PKF/PD, F Hoffmann-La Roche Ltd, Basle, Switzerland aut NATIONALLICENCE 700 1- Lücker P. Institut für Klinische Pharmakologie, Bobenheim, Grunstadt, FRG aut NATIONALLICENCE 773 0- European Journal of Drug Metabolism and Pharmacokinetics Springer-Verlag 15/4(1990-10-01), 317-322 0378-7966 15:4<317 1990 15 13318 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer