Population pharmacokinetic modelling and simulation of single and multiple dose administration of meloxicam in cats.
The objectives of these investigations were: first, to describe the pharmacokinetic properties of meloxicam in cats following single and multiple oral administration and secondly, to simulate different oral dosage regimes for meloxicam in cats after multiple dose administration to illustrate and evaluate those dosage regimes for the alleviation of inflammation and pain in cats. Six healthy domestic short hair cats were treated orally with various dosage regimes (0.05-0.2 mg/kg/day). Plasma samples were collected at predefined times and quantitatively analysed using liquid/liquid extraction followed by reverse phase HPLC with UV-detection. Meloxicam plasma concentration data were analysed using the population pharmacokinetic approach (software: NONMEM). The final model was used to simulate different dosage regimes. The plasma concentration-time profiles of meloxicam in cats after oral single and multiple dose administration were best described by an open one-compartment model with first-order absorption and first-order elimination. Pharmacokinetic parameters were estimated to be 0.00656 L/h/kg for the total apparent body clearance (CL/F), 0.245 L/kg for the apparent volume of distribution (V/F), 1.26 1/h for the absorption constant (K(A)) and 25.7 h for the mean plasma terminal half-life. Simulations showed that the median trough steady-state concentrations of 228 ng/mL were reached after five, one or 6 days following a single initial dose of 0.05, 0.1 and 0.2 mg/kg each followed by 0.05 mg/kg/day.
Lehr
T
T
Department of Clinical Pharmacy, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany. thorsten.lehr@boehringer-ingelheim.com
Narbe
R
R
Jöns
O
O
Kloft
C
C
Staab
A
A
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002415:Cats; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule / Q000662:veterinary; D005260:Female; D006207:Half-Life; D008297:Male; D000077239:Meloxicam; D008954:Models, Biological; D013843:Thiazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013844:Thiazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam