Relationship between paracetamol plasma levels and its analgesic effect in the rat.
The relationship between plasma levels of paracetamol and its analgesic effect was studied in the rat using a model of pain-induced functional impairment (PIFI). Female Wistar rats received an intraarticular injection of 30% uric acid in the knee of the right hind limb, inducing its dysfunction. Animals then received oral paracetamol at doses of 178, 316 or 562 mg kg-1 and the recovery of functionality over time was considered as an expression of analgesia. Paracetamol plasma levels were determined by HPLC. Results showed that there is a direct relationship between paracetamol plasma levels and its analgesic effect that follows a sigmoidal model according to the Hill equation. The PIFI model appears to be a useful tool to establish pharmacokinetic/pharmacodynamic relationships for non-narcotic analgesics.
Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, DF.
V
V
Granados-Soto
F J
FJ
Flores-Murrieta
F J
FJ
López-Muñoz
L A
LA
Salazar
J E
JE
Villarreal
G
G
Castañeda-Hernández
D000082:Acetaminophen / Q000097:blood* / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008954:Models, Biological; D009619:Nociceptors / Q000187:drug effects; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar
D000700:Analgesics; D000082:Acetaminophen