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The influence of hemorrhagic shock on the pharmacokinetics and the analgesic effect of morphine in the rat
Author(s) -
Paepe P,
Belpaire FM,
Rosseel MT,
Buylaert WA
Publication year - 1998
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1998.tb00996.x
Subject(s) - morphine , analgesic , pharmacokinetics , volume of distribution , bolus (digestion) , pharmacology , metabolite , shock (circulatory) , distribution (mathematics) , intravenous bolus , chemistry , medicine , anesthesia , endocrinology , mathematical analysis , mathematics
Summary— 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.