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Oral bioavailability of P‐glycoprotein substrate drugs do not differ between ABCB 1‐1Δ and ABCB 1 wild type dogs
Author(s) -
MEALEY K. L.,
WAITING D.,
RAUNIG D. L.,
SCHMIDT K. R.,
NELSON F. R.
Publication year - 2010
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2010.01170.x
Subject(s) - bioavailability , pharmacokinetics , pharmacology , p glycoprotein , medicine , chemistry , multiple drug resistance , biochemistry , antibiotics
Mealey, K.L., Waiting, D., Raunig, D.L., Schmidt, K.R., Nelson, F.R. Oral bioavailability of P‐glycoprotein substrate drugs do not differ between ABCB 1‐1Δ and ABCB 1 wild type dogs. J. vet. Pharmacol. Therap . 33 , 453–460. Previous studies have indicated that intestinal P‐glycoprotein (P‐gp) limits the oral bioavailability of substrate drugs and alters systemic pharmacokinetics. In this study, dogs lacking functional P‐gp were used to determine the contribution of P‐gp to the oral bioavailability and systemic pharmacokinetics of several P‐gp substrate drugs. The P‐gp substrates quinidine, loperamide, nelfinavir, cyclosporin and the control (non P‐gp substrate) drug diazepam were individually administered intravenously and per os to ABCB 1‐1Δ dogs, which have a P‐gp null phenotype and ABCB 1 wildtype dogs. ABCB 1‐1Δ dogs have been shown to have greater brain penetration of P‐gp substrates, but limited information is available regarding oral bioavailability of P‐gp substrate drugs in this animal model. Plasma drug concentration vs. time curves were generated and pharmacokinetic parameters were calculated for each drug. There were no differences in oral bioavailability between ABCB 1‐1Δ dogs and ABCB 1 wildtype dogs for any of the drugs studied, suggesting that intestinal P‐gp does not significantly affect intestinal absorption of these particular substrate drugs in ABCB1‐1Δ dogs. However, small sample sizes and individual variability in CYP enzyme activity may have affected the power of the study to detect the impact of P‐gp on oral bioavailability.