The influence of renal function on the renal clearance of morphine and its glucuronide metabolites in intensive‐care patients.

Abstract

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 (CLCr, meas) was calculated from plasma and urinary creatinine concentrations (from h.p.l.c.). Also, creatinine clearance was predicted (CLCr, pred) from routine laboratory determination of plasma creatinine (Jaffe method). 3. There were significant linear relationships (P less than 0.001) between CLCr, meas and the renal clearances of morphine, M3G and M6G. The unbound renal clearance of morphine exceeded CLCr, meas (P less than 0.002) while the unbound renal clearances of M3G and M6G did not differ from CLCr, meas (P greater than 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 CLCr, pred. Significant (P less than 0.001) relationships were observed between the reciprocal of CLCr, 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.

Pharmacokinetics of Morphine and Its Metabolites in Infants and Young Children After Congenital Heart Surgery

“…It is well established from literature data that clearance of M3G and M6G is influenced by renal function in diverse populations (36)(37)(38). In this study, we were able to detect a correlation between GFR and both metabolite formation time delay and maximum concentrations (Fig.…”

Effects of Hypothermia on the Disposition of Morphine, Midazolam, Fentanyl, and Propofol in Intensive Care Unit Patients

“…Reduced renal function is known to increase morphine glucuronide/morphine ratios (Faura et al, 1998). Second, the 50% reduction of creatinine clearance, a strong predictor of the renal clearances of morphine metabolites (Milne et al, 1992), suggests a reduction in renal excretion of M3G and M6G resulting in accumulation of these metabolites in serum. However, the The PK of midazolam in the control group were similar to that described previously in critically ill patients (Løvstad et al, 1996).…”

Opioids and renal function

“…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 patients in intensive care. 101 The pharmacokinetics of morphine and its glucuronide metabolites were investigated in 3 groups of patients with kidney failure (nondialyzed, receiving dialysis, and transplantation) undergoing surgical procedures and compared with a group of volunteers. Patients with kidney failure had a significantly increased morphine AUC compared with control subjects.…”