The influence of hemorrhagic shock on the pharmacokinetics and the analgesic effect of morphine in the rat.
The influence of hemorrhagic shock (removal of 30% of the blood volume) on the pharmacokinetics and the analgesic effect of morphine was investigated in conscious rats. Plasma concentrations of morphine after a bolus injection (5 mg/kg) are higher in the shock animals, which is attributed to a small decrease in clearance (-22%; P > 0.05) and a significant decrease in distribution volume (-33%; P < 0.05) of the drug. The areas under the plasma concentration-time curve of the metabolite morphine-3-glucuronide (M3G) are significantly higher (+237%; P < 0.01) in the shock rats, which is probably explained by a decreased distribution and renal excretion. The analgesic effect of morphine was evaluated using the tail-flick test during a continuous infusion (10 mg/kg/h) with measurement of the plasma concentrations of morphine and M3G. Data from these experiments show higher plasma concentrations of morphine (+33%; P < 0.05) and M3G (+66%; P > 0.05) during shock, and a significantly increased analgesic effect (+43%; P < 0.05). Our data suggest that the increased analgesic effect of morphine during hemorrhagic shock can most likely be explained by pharmacokinetic changes resulting in higher morphine concentrations.
De Paepe
P
P
Heymans Institute of Pharmacology, University of Gent, Medical School, Belgium.
Belpaire
F M
FM
Rosseel
M T
MT
Buylaert
W A
WA
D000698:Analgesia; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D007275:Injections, Intravenous; D008297:Male; D009020:Morphine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000097:blood; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D013997:Time Factors
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; D009020:Morphine; C018108:morphine-3-glucuronide