Regional blood flow as a determinant of drug absorption description of an animal model.
Factors that influence recommended dosage guidelines for intramuscularly and subcutaneously injected drugs include a spectrum of variables, including therapeutic objective(s), the drug's therapeutic index, the inclusion of concomitant vasoconstrictors, and so on. However, little account is taken of the likely influence of regional blood flow at the injection site. This may vary according to the site of injection, the age and medical condition of the patient with the potential to markedly affect the rate of drug absorption and the resultant therapeutic and toxicity outcomes. An animal model is described for simultaneously quantifying the drug's pharmacokinetic profile and the regional blood flow (using technetium99 elution) at sites of differing vascularity so that the potential relationship can be ascertained. An application to lignocaine absorption is provided, however, the model would be applicable to a range of drug applications and could serve as a means of investigating differences both within a drug class (e.g., members with differing lipophilicity) as well as across drug classes (e.g., local anesthetics, opiates, insulin preparations, etc.).
Morris
R G
RG
Department of Clinical Pharmacology, Queen Elizabeth Hospital, Woodville, South Australia.
Karatassas
A
A
Orfanos
A
A
D000768:Anesthesia, General; D000818:Animals; D001784:Blood Gas Analysis; D006439:Hemodynamics / Q000502:physiology; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008012:Lidocaine / Q000493:pharmacokinetics; D008954:Models, Biological; D010599:Pharmacokinetics; D010865:Pilot Projects; D012039:Regional Blood Flow / Q000502:physiology*; D012756:Sheep; D013670:Sodium Pertechnetate Tc 99m
D008012:Lidocaine; D013670:Sodium Pertechnetate Tc 99m