Intravenous versus subcutaneous injections of apomorphine in rabbits: a pharmacokinetic paradox

The objective of this investigation was an attempt to conclusively prove the accidental observation that the AUC of apomorphine in rabbits was repeatedly lower after intravenous injection compared to subcutaneous injection. Apomorphine was administered to rabbits by intravenous and subcutaneous routes at 2 different doses (0.31 mg/kg, n=10; and 0.25 mg/kg, n=6). Plasma drug concentrations were measured by HPLC-ECD and pharmacokinetic parameters were estimated by compartmental and non-compartmental approaches. The AUC of apomorphine in rabbits were: for subcutaneous injection, 14138 +/- 502 ng/ml/min and 12680 +/- 855 ng/ml/min, n=10 and 6, respectively; for intravenous injection, 11850 +/- 718 ng/ml/min and 9147 +/- 671 ng/ml/min, n=10 and 6, respectively. These AUC values were statistically significantly lower when given as intravenous injection compared to subcutaneous injection (p=0.0011 and 0.0117, n=10 and 6, respectively). The T1/2,elim values were: for subcutaneous injection, 17.1 +/- 1.70 min and 18.7 +/- 1.68 min, n=10 and 6, respectively; for intravenous injection, 15.3 +/- 1.20 min and 15.0 +/- 2.24 min, n=10 and 6, respectively. There were no significant differences between the T1/2,elim from both administration routes (p=0.3984 and 0.2158, n=10 and 6, respectively). Given the reproducibility of the results, it was concluded that the AUC of apomorphine after intravenous injection in rabbits is anomalously lower than that of subcutaneous injection.