Pharmacokinetics and tolerability of meloxicam after i.m. administration.
1. The pharmacokinetics and tolerability of a new nonsteroidal anti-inflammatory drug (NSAID), meloxicam, administered i.m., were investigated in two studies conducted in healthy male volunteers. Study 1 was an open, placebo-controlled design in which 32 volunteers were randomized to a single ascending i.m. dose of meloxicam (5, 10, 20, and 30 mg) or placebo. Study 2 had an open, randomized two way crossover design in which 12 volunteers received single i.m. and i.v. doses of meloxicam (15 mg). 2. Meloxicam showed an excellent tolerability in both studies. No effect was seen on serum creatinphosphokinase (CK, the isoenzyme of the skeletal muscle enzyme, CK-MM, was determined). 3. Following i.m. administration meloxicam was rapidly and completely absorbed (mean absolute bioavailability 102%). Dose-proportionality was demonstrated with respect to Cmax (maximum plasma concentration) and AUC (extrapolated area under the plasma concentration-time curve from zero time to infinity) over a range of 5-30 mg. 4. Intravenous administration of meloxicam (15 mg) resulted in higher initial plasma concentrations (C3min, i.e. concentration in plasma 3 min after start of injection = 2.99 +/- 0.75 microgram.ml-1) than after i.m. injection (Cmax: 1.62 +/- 0.20 mg ml-1). All other pharmacokinetic parameters were similar for both routes of administration (apparent elimination half-life = 15-22 h; plasma clearance = 7-9 ml min-1). 5. In conclusion, the excellent tolerability of i.m. meloxicam together with its rapid and complete absorption may provide an alternative to oral administration of this drug.
Narjes
H
H
Department of Pharmacokinetics and Drug Metabolism, Human Pharmacology Centre, Germany.
Türck
D
D
Busch
U
U
Heinzel
G
G
Nehmiz
G
G
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D000077239:Meloxicam; D008875:Middle Aged; D012016:Reference Values; D013843:Thiazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam