Population pharmacokinetic modelling and simulation of single and multiple dose administration of meloxicam in cats

Abstract

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.

Bioavailability and pharmacokinetics of oral meloxicam in llamas

“…The most closely related species studied thus far has been camels, however, only IV administration was evaluated in that study. The half-life of oral meloxicam in llamas (22.7 hrs) appears to be similar to species such as cattle (27.5 hrs) [18] and cats (24 hrs) [23] but is much slower than in other species such as goats (11.8 hrs) [19] and dogs (12.1 hrs) [24]. In contrast, T MAX exhibits extreme variation, with llamas taking the longest time to reach maximum concentration (21.4 hrs) and horses the shortest (1.5 hrs) [20].…”

Postoperative analgesic efficacy of meloxicam compared to tolfenamic acid in cats undergoing orthopaedic surgery

“…Meloxicam is licensed for acute and chronic use in cats in many countries and has been shown to be effective in cats both for perioperative (Slingsby and Waterman‐Pearson 2000, 2002, Carroll and others 2005, Gassel and others 2005) and long‐term use to treat painful locomotor disorders (Lascelles and others 2001, Clarke and Bennett 2006, Gunew and others 2008). Meloxicam is a preferential COX‐2 inhibitor and its pharmacokinetics in cats have been described following single subcutaneous (Giraudel and others 2005) and repeated oral (Lehr and others 2009) administration.…”

Exploring Population Pharmacokinetic Modeling with Resampling Visualization

“…Resampling techniques, based on the intensive computational capacity of computers, have been widely applied to PopPK modeling for the assessment of uncertainty in parameter estimations and the detection of influential observations [9–12]. Though hundreds or thousands of data sets are produced with resampling, users generally tend to examine the numerical rather than the graphical summaries.…”