clindamycin-phosphate and Kidney-Failure--Chronic

We evaluated the pharmacokinetics of clindamycin and the dose of clindamycin phosphate necessary to treat peritonitis after intraperitoneal administration of clindamycin phosphate to patients on continuous ambulatory peritoneal dialysis (CAPD). This was an open-label, prospective, single-dose study conducted at the two levels of institutional clinical care in South Korea. Twelve patients (six men and six women; all older than 25 years), mean CAPD duration of 38.2 months with various origins without peritonitis, received 600 mg clindamycin phosphate mixed with only the first 2-L dialysate (1.5% dextrose). The 1.5%, 1.5%, 2.5% and 1.5% dextrose dialysates were serially exchanged every 6 hr. If patients were non-anuric, 24-hr urine samples were also collected. Clindamycin phosphate was incompletely activated to clindamycin in the dialysate. The clindamycin concentration in the dialysate was greater than the effective concentration (5 μg/mL) at 6.87 μg/mL up to 6 hr. So, 600 mg clindamycin phosphate per every 6 hr dialysate is effective for treatment of peritonitis. It has been reported that the clindamycin concentrations in the dialysate may be higher in CAPD patients with peritonitis. Thus, we can expect that intraperitoneal administration of <600 mg clindamycin phosphate per every 6 hr dialysate could be maintained over 5 μg/mL in patients with peritonitis. The transfer of clindamycin was unidirectional from the dialysate to the plasma.

Topics: Adult; Aged; Anti-Bacterial Agents; Clindamycin; Dialysis Solutions; Drug Dosage Calculations; Female; Humans; Infusions, Parenteral; Kidney Failure, Chronic; Male; Middle Aged; Models, Biological; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Prospective Studies; Republic of Korea; Treatment Outcome

The kinetics of intraperitoneally administered clindamycin phosphate were studied in 9 volunteer subjects undergoing CAPD. Volunteers were assigned to 2 groups with the first group receiving clindamycin phosphate 300 mg/l in exchanges 1 through 5, and the second group receiving clindamycin phosphate 300 mg/l in exchange 1, and then 30 mg/l in exchanges 2 through 5. Clindamycin serum and dialysate effluent levels were determined by bioassay. When admixed with dialysate fluid and instilled into the peritoneal cavity, clindamycin phosphate is rapidly activated. Serum concentrations of clindamycin were rapidly achieved in both groups during the first exchange. Subjects in groups I and II had peak serum levels of active drug within 3 (3.94 ug/ml) and 5 (7.35 ug/ml) h, respectively. These results support the practice of not only administering intraperitoneal clindamycin phosphate to treat CAPD-related peritonitis, but using this route of administration to treat systemic infections due to susceptible bacteria in patients without intravenous access.

Topics: Adult; Aged; Body Fluids; Clindamycin; Female; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory

Clindamycin phosphate (C-PO4) must be hydrolyzed to the active antibiotic, but whether this occurs within the peritoneal cavity during peritoneal dialysis is unknown. Therapeutic peritoneal levels are difficult to achieve after intravenous administration, so direct intraperitoneal instillation is preferred in treating dialysis-associated peritonitis. Therefore, the activation of C-PO4 in peritoneal dialysate was investigated. Fresh and 'uremic' peritoneal dialysates of 1.5 and 4.25% dextrose concentrations at pHs of 5.1 and 7.4 did not activate C-PO4. Clindamycin hydrochloride in this same fluid was active, ruling out uremic deactivators. A patient with peritonitis was treated with intraperitoneal C-PO4, and therapeutic (greater than 5 micrograms/ml) serum and peritoneal levels were achieved. Infected (exudative) peritoneal dialysate drained from another patient with peritonitis activated C-PO4 in vitro. Commercial alkaline phosphatase added to uremic dialysate also activated C-PO4 in vitro. C-PO4 was instilled into the peritoneal cavities of 10 noninfected patients. Exposure to the peritoneal membrane at two concentrations resulted in a 3% activation of C-PO4. From these observations it is clear that C-PO4 is only partially activated intraperitoneally. Uremia or uremic products in the dialysate do not deactivate the antibiotic. Exudative material (bacteria, white blood cells and proteins) in infected dialysate contribute to activation of C-PO4. The peritoneal membrane further assists in activation. We recommend that C-PO4 be administered at a concentration of 167 mg/l of dialysate to ensure therapeutic peritoneal levels of the active antibiotic, especially after the exudative phase clears.

Topics: Alkaline Phosphatase; Biological Availability; Clindamycin; Humans; Hydrolysis; Kidney Failure, Chronic; Peritoneal Cavity; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis