Pharmacokinetic-pharmacodynamic modelling of meperidine in goats (I): Pharmacokinetics.
Plasma and cerebrospinal fluid (CSF) pharmacokinetics of meperidine were investigated after intramuscular (i.m.) or intravenous (i.v.) administration at a dose of 5 mg/kg in adult goats. After i.m. dosing, the plasma profile was best described by a one-compartment open model. In healthy (n = 16) and post-operative (n = 16) goats, the parameters were, respectively: tmax 8.3 +/- 3.9 and 9.2 +/- 5.5 min, Vd 2.763 +/- 1.231 and 3.929 +/- 2.101 l/kg, Clb 0.125 +/- 0.036 and 0.087 +/- 0.025 l/kg/min, Ke 0.0563 +/- 0.0358 and 0.0271 +/- 0.0136 min-1. The plasma profile was best fitted by a two-compartment open model following i.v. injection. In this case, the parameters for healthy (n = 7) and post-operative (n = 13) goats were, respectively: Vd 5.212 +/- 1.992 and 5.085 +/- 2.288 l/kg, Clb 0.096 +/- 0.028 and 0.075 +/- 0.026 l/kg/min, beta 0.0211 +/- 0.0093 and 0.0160 +/- 0.0052 min-1. There were, however, a few individuals with a prolonged elimination phase. Bioavailability of i.m. meperidine was 66.5 +/- 15.8% in healthy (n = 6) goats, but much higher in postoperative (n = 10) ones at 94.6 +/- 30.0%. Meperidine diffused into and out of CSF according to a first-order rate process. The time-course of CSF drug concentration was simulated by a biexponential function. CSF kinetic parameters of i.m. meperidine for healthy (n = 7) and postoperative (n = 13) goats were: elimination rate constant (K(ef)) 0.0269 +/- 0.0131 and 0.0305 +/- 0.0177 min-1, peak CSF concentration time (Tmaxf) 15.9 +/- 5.0 and 17.0 +/- 6.9 min. For the i.v. dosed healthy (n = 6) and postoperative (n = 8) animals, K(ef) was 0.0408 +/- 0.0107, 0.0414 +/- 0.0123 min-1 and Tmaxf was 10.0 +/- 5.0 and 7.7 +/- 2.5 min, respectively. It was demonstrated that an obviously lower peak concentration can be reached significantly later in CSF than in plasma, and the kinetic behaviour of meperidine in plasma is different from that in the CSF, indicating meperidine analgesia might not be predicted by simple extrapolation from the kinetic data.
Qiao
G L
GL
Laboratory of Veterinary Pharmacology, South China Agricultural University, Guangzhou.
Fung
K F
KF
D000818:Animals; D001682:Biological Availability; D002849:Chromatography, Gas / Q000662:veterinary; D005260:Female; D006041:Goats / Q000378:metabolism*; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D008614:Meperidine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008954:Models, Biological
D008614:Meperidine