Oral paracetamol bioavailability in rats subjected to experimental spinal cord injury.
The purpose of the present study was to examine the time dependence of oral paracetamol (acetaminophen) bioavailability in an experimental model of spinal cord injury (SCI). Female Sprague-Dawley rats were subjected to spinal cord contusion at the T8-T9 level by the weight drop method producing permanent paraplegia. Oral paracetamol bioavailability after administration of a single 100 mgkg-1 dose was determined 1, 12, and 50 d after SCI. Cmax and AUC were significantly decreased 1 d after SCI compared to sham-injured controls. This reduction, however, was temporary, as there was a recovery of bioavailability parameters which was partial 12 d after SCI, being complete by day 50. The present results confirm the usefulness of animal models for the characterization of the effect of SCI in drug kinetics. Data show that SCI induces significant changes in paracetamol pharmacokinetics. Nonetheless, despite the fact of a permanent loss of functions related to locomotion, pharmacokinetic alterations evolved with time.
García-López
P
P
Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, D. F., Mexico.
Pérez-Urizar
J
J
Madrazo
I
I
Guízar-Sahagún
G
G
Castañeda-Hernández
G
G
D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D009043:Motor Activity / Q000187:drug effects; D010264:Paraplegia / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen