Comparative study of the pharmacokinetics of alfentanil in rabbits, sheep, and dogs

Jan E. Ilkiw From the Department of Surgery, School of Veterinary Medicine (Ilkiw, McNeal) and the Department of Anesthesiology (Benthuysen), University of California, Davis, CA 95616.

Search for other papers by Jan E. Ilkiw in
Current site
Google Scholar
PubMed
Close
 PhD, BVSc
,
James A. Benthuysen From the Department of Surgery, School of Veterinary Medicine (Ilkiw, McNeal) and the Department of Anesthesiology (Benthuysen), University of California, Davis, CA 95616.

Search for other papers by James A. Benthuysen in
Current site
Google Scholar
PubMed
Close
 MD
, and
D. McNeal From the Department of Surgery, School of Veterinary Medicine (Ilkiw, McNeal) and the Department of Anesthesiology (Benthuysen), University of California, Davis, CA 95616.

Search for other papers by D. McNeal in
Current site
Google Scholar
PubMed
Close

Click on author name to view affiliation information

SUMMARY

The central arterial pharmacokinetics of alfentanil, a short-acting opioid agonist, were studied in rabbits, sheep, and dogs after short-duration infusion of the drug. Alfentanil was infused until a set end point (high-amplitude, slow-wave activity on the eeg) was reached. This required a larger alfentanil dose and a higher alfentanil arterial concentration in sheep, compared with rabbits and dogs. The plasma concentration-time data for each animal were fitted, using nonlinear regression, and in all animals, were best described by use of a triexponential function. In this study, differences in the disposition kinetics of alfentanil among the 3 species were found for only distribution clearance and initial distribution halflife. In dogs, compared with rabbits and sheep, the first distribution half-life was longer, probably because of pronounced drug-induced bradycardia (mean ± SD, 48 ± 21 beats/min). Distribution clearance was faster in sheep, compared with dogs, also probably because of better blood flow in sheep. Elimination half-life was similar in all species (rabbits, 62.4 ± 11.3 minutes; sheep, 65.1 ± 27.1 minutes; dogs, 58.3 ± 10.3 minutes). This rapid half-life resulted from a small steady-state volume of distribution (rabbits, 908.3 ± 269.0 ml/kg; sheep, 720.0 ± 306.7 ml/ kg; dogs, 597.7 ± 290.2 ml/kg) and rapid systemic clearance (rabbits, 19.4 ± 5.3 ml/min/kg; sheep, 13.3 ± 3.0 ml/min/kg; dogs, 18.7 ± 7.5 ml/min/kg). On the basis of these pharmacokinetic variables, alfentanil should have short duration of action in rabbits, sheep, and dogs. This may be beneficial in veterinary practice where rapid recovery would be expected after bolus administration for short procedures or after infusion for longer procedures.

SUMMARY

The central arterial pharmacokinetics of alfentanil, a short-acting opioid agonist, were studied in rabbits, sheep, and dogs after short-duration infusion of the drug. Alfentanil was infused until a set end point (high-amplitude, slow-wave activity on the eeg) was reached. This required a larger alfentanil dose and a higher alfentanil arterial concentration in sheep, compared with rabbits and dogs. The plasma concentration-time data for each animal were fitted, using nonlinear regression, and in all animals, were best described by use of a triexponential function. In this study, differences in the disposition kinetics of alfentanil among the 3 species were found for only distribution clearance and initial distribution halflife. In dogs, compared with rabbits and sheep, the first distribution half-life was longer, probably because of pronounced drug-induced bradycardia (mean ± SD, 48 ± 21 beats/min). Distribution clearance was faster in sheep, compared with dogs, also probably because of better blood flow in sheep. Elimination half-life was similar in all species (rabbits, 62.4 ± 11.3 minutes; sheep, 65.1 ± 27.1 minutes; dogs, 58.3 ± 10.3 minutes). This rapid half-life resulted from a small steady-state volume of distribution (rabbits, 908.3 ± 269.0 ml/kg; sheep, 720.0 ± 306.7 ml/ kg; dogs, 597.7 ± 290.2 ml/kg) and rapid systemic clearance (rabbits, 19.4 ± 5.3 ml/min/kg; sheep, 13.3 ± 3.0 ml/min/kg; dogs, 18.7 ± 7.5 ml/min/kg). On the basis of these pharmacokinetic variables, alfentanil should have short duration of action in rabbits, sheep, and dogs. This may be beneficial in veterinary practice where rapid recovery would be expected after bolus administration for short procedures or after infusion for longer procedures.

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 59 59 11
PDF Downloads 36 36 11
Advertisement