THE INFLUENCE OF RENAL-FUNCTION ON THE RENAL CLEARANCE OF MORPHINE AND ITS GLUCURONIDE METABOLITES IN INTENSIVE-CARE PATIENTS

1 The relationships between renal creatinine clearance and the renal clearances of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were studied in fifteen intensive-care patients who were receiving morphine sulphate by constant intravenous infusion and who had diverse renal function. 2 An arterial blood sample was collected before and after a 4-5 h urine collection. Plasma and urine concentrations of morphine, M3G and M6G were measured by h.p.l.c. Plasma binding of all three compounds in drug-free plasma from healthy volunteers was determined by ultrafiltration. Measured renal creatinine clearance (CL(Cr,meas)) was calculated from plasma and urinary creatinine concentrations (from h.p.l.c.). Also, creatinine clearance was predicted (CL(Cr,pred)) from routine laboratory determination of plasma creatinine (Jaffe method). 3 There were significant linear relationships (P < 0.001) between CL(Cr,meas) and the renal clearances of morphine, M3G and M6G. The unbound renal clearance of morphine exceeded CL(Cr,meas) (P < 0.002) while the unbound renal clearances of M3G and M6G did not differ from CL(Cr,meas) (P > 0.5). 4 In ten of the patients who received a constant infusion of morphine for at least 6 h, the dose-normalised plasma concentrations of M3G and M6G increased with decreasing CL(Cr,pred). Significant (P < 0.001) relationships were observed between the reciprocal of CL(Cr,pred) and the dose-normalised plasma concentrations of M3G and M6G. 5 The results indicate the importance of renal function in determining the renal clearances and plasma concentrations of M3G and M6G during intravenous infusion with morphine in intensive-care patients.