The effect of anesthesia on the pharmacokinetics of sublingually administered verapamil in rabbits

✍ Scribed by Paul A. Moench; Christopher L. Heran; Paul I. Stetsko; Neil R. Mathias; Doris A. Wall; Munir A. Hussain; Ronald L. Smith

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 67 KB
• Volume: 92
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.10436

✦ Synopsis

The systemic bioavailability of the calcium channel blocker verapamil HCl after sublingual (SL) administration has been clinically demonstrated. [1][2][3][4][5] Therefore, this compound was chosen as a model compound for evaluation during establishment of a preclinical rabbit model for intra-oral drug delivery. Unlike human subjects, rabbits are often anesthetized to minimize drug swallowing and to ensure accurate intra-oral delivery of the dose. Because there are many available methods and types of general anesthesia, and certain anesthetics are known to affect salivary flow and hemodynamics, 6 there was a need to understand how this variable may impact the preclinical pharmacokinetic (PK) analysis and the extrapolation to data obtained in human subjects. To our knowledge, there have been no reported studies on the effects of general anesthesia on the bioavailability of a SL administered drug in rabbits. This study addressed this concern by investigating the effect(s) of the long-acting intramuscularly administered ketamine/xylazine (Ketaset TM / Rompum TM ) versus the short-acting inhalational anesthetic isoflurane (Aerrane TM ) on the PK profile of SL administered verapamil in rabbits. Three groups of vascular access ported White New Zealand rabbits (3-5 animals/group; mean