Pharmacokinetics of morphine sulfate in patients with burns

Morphine sulfate (MS) pharmacokinetics was evaluated in seven patients with a mean body surface area burn of 21.5% to ascertain a rational basis for the management of pain in patients with burns. Treatments included a MS constant rate infusion followed by an oral MS solution (MS-OS) (5 to 15 mg administered every 3 hours) and then a 30 mg MS-controlled release tablet (MS-CR) every 8 hours. Each treatment was separated by a washout period when sampling of morphine was done. The apparent terminal half-life for MS-OS was 3 hours, which is similar to that of patients without burns, but the apparent terminal half-life for the MS-CR in patients with burns was substantially longer at 14.7 hours. The mean time to reach peak concentration for MS-CR was delayed relative to MS-OS 1.4 versus 0.5 hours, and the peak concentration was attenuated. The mean release time of the MS for the CR tablet is about 15 hours. The renal clearances of the MS-CR (114 ml/min) and MS-OS (147 ml/min) were less than the measured creatinine clearance (177 ml/min) but greater than the creatinine clearance (106 ml/min) predicted for a healthy individual. The prolonged release of MS-CR makes the MS-CR a good choice in the management of pain in patients with burns on an 8- to 12-hour dosing schedule, even though the patient might exhibit an increased clearance.