PHARMACOKINETICS OF CLOXACILLIN IN PATIENTS UNDERGOING HIP OR KNEE REPLACEMENT

Objective: The pharmacokinetics of cloxacillin was investigated in 14 men and 24 women undergoing cemented hip (n = 19; age range 56-90) or knee replacement surgery (n = 19; age range 51-84) for osteoarthritis. Cloxacillin 1 g was given intravenously as a bolus dose at the induct ion of anesthesia, and plasma samples and urine were collected for 6 h . Drug levels were determined using HPLC. Results: Preoperative serum creatinine levels were 84 mu mol.l(-1) in hip patients and 72 mu mol.l (-1) in knee patients. The calculated values for creatinine clearance were 63 and 85 ml.min(-1) 1.73 m(-2), respectively. Total clearance of cloxacillin was 134 ml.min(-1).1.73 m(-2) in eighteen evaluated patie nts undergoing hip replacement, and 162 ml.min(-1).1.73 m(-2) in eight een patients undergoing knee surgery. Renal clearance was 72 and respe ctively. Non-renal clearance was 57 ml.min(-1).1.73 m(-2) in hip patie nts and 77 ml.min(-1).1.73 m(-2) in knee patients. Renal clearance of cloxacillin correlated with the estimated creatinine clearance (r = 0. 652). Although women received higher doses than men (median 2.02 vs 2. 32 mmol.1.73 m(-2)), there were no sex differences in clearance correc ted for body surface area. Conclusion: Total clearance of cloxacillin was lower in patients undergoing hip replacement than in patients unde rgoing replacement of the knee, but there was no difference between me n and women.