Summary
The pharmacokinetics of the fixed combination trimethoprim sulfamethoxazole (TMP — SMZ), including peritoneal transfer, has been studied in patients with end-stage renal disease treated by peritoneal dialysis, intermittent in 18 cases and continuous ambulatory dialysis in 6 cases. After a single oral dose of TMP 4mg and SMZ 20mg per kg, peak serum levels of approximately 2.0 µg/ml TMP and 28 µg/ml SMZ were achieved at 4hours for TMP, and at 6 hours for SMZ. The protein binding of TMP was 34.7±1.1% and its distribution volume was 2.2±0.51/kg. Total plasma clearance of TMP was 66.2±11.5ml/min, peritoneal dialysance was 5.1±0.5ml/min, and renal clearance was negligible. The protein binding of SMZ was 48.0 ±1.4% and the distribution volume was 0.55±0.071/kg. Total plasma clearance of SMZ was 26.2±5.7ml/min, peritoneal dialysance was 1.2±0.2ml/min, and renal clearance was negligible. The half lives of TMP and SMZ were 23.7±4.0h and 18.1±3.5h, respectively. The peritoneal dialysance both of TMP and SMZ after oral administration was very low. In contrast the absorption after intra-peritoneal administration is high. Peritoneal absorption was increased during peritonitis. In patients with peritonitis, the intra-peritoneal administration of TMP-SMZ resulted in an immediate high local concentration, and a serum concentration of both drugs in the therapeutic range within 6 to 12h.
Similar content being viewed by others
References
Tenckhoff H (1974) Chronic peritoneal dialysis manual. University of Washington, Seattle
Popovich RP, Moncrief JW, Nolph KD, Ghods AJ, Twardowski ZJ, Pyle WK (1978) Continuous ambulatory peritoneal dialysis. Ann Intern Med 88: 449–456
Legrain M (ed) (1979) Continuous ambulatory peritoneal dialysis: First international Symposium, Paris, Excerpta Medica, Amsterdam
Moncrief, JW (ed) (1979) Continuous ambulatory peritoneal dialysis. Second International Symposium, Austin Excerpta Medica, Amsterdam
Rubin J, Rogers WA, Taylor HM, Everett ED, Prowant BF, Fruto LV, Nolph KD (1980) Peritonitis during continuous ambulatory peritoneal dialysis. Ann Intern Med 92: 7–13
Oreopoulos DG, Robson M, Izatt S, Clayton S, de Veber GA (1978) A simple and safe technique for continuous ambulatory peritoneal dialysis (CAPD). Trans Am Soc Artif Intern Organs 24: 484–489
Renaux C, Certain B, Mollet M, Rottembourg J (1980) La dialyse péritonéale continue ambulatoire. I, Le matériel et la technique. Nouv Presse Med 42: 3155–3158
Schwartz DE, Koechlin BA, Weinfeld RE (1969) Spectrofluorometric method for the determination of trimethoprim in body fluids. Chemotherapy 14: 22–29
Bratton AC, Marshall EK (1939) A new coupling component for sulfonamide determination. J Biol Chem 198: 537–541
Rieder (1972) Quantitative determination of bacteriostatically active fraction of sulfonamides and the sum of their inactive metabolites in the body fluids. Chemotherapy 17: 1–21
Brumfitt W, Hamilton-Miller JMT, Kosmidis J (1973) Trimethoprim Sulfamethoxazole: The present position. J Infect Dis 128: 778–791
Rieder J, Schwartz DE, Fernex M, Bergan I, Brodwall EK, Blumberg A, Cottier P, Scheitlin W (1974) Pharmacokinetics of the antibacterial combination sulfamethoxazole plus trimethoprim in patients with normal or impaired kidney function. Antibiot Chemother 18: 148–198
Gibson TP, Matusik E, Nelson LD, Briggs WA (1976) Artificial kidney and clearance calculations. Clin Pharmacol Ther 20: 720–726
Baethke R, Golde G, Gahl G (1972) Sulfamethoxazole — Trimethoprim: pharmacokinetic studies in patients with chronic renal failure. Eur J Clin Pharmacol 4: 233–240
Bergan T, Brodwall EK (1972) Kidney transport in man of sulfamethoxazole and trimethoprim. Chemotherapy 17: 320–333
Craig WA, Kunin CM (1973) Trimethoprim-Sulfamethoxazole: Pharmacodynamic effects of urinary pH and impaired renal function. Ann Intern Med 78: 491–497
Reeves DS, Wilkinson PJ (1979) The pharmacokinetic of trimethoprim and trimethoprim-sulfonamide combination including penetration in body tissues. Infection 7: S330-S341
Vree TB, Hekster YA, Baars AM, Dansma JE, van der Kleijn E (1978) Pharmacokinetics of sulfamethoxazole in Man. Clin Pharmacokinet 3: 319–329
Tasker PRW, Mac Gregor GA, de Wardener HE (1975) Use of co-trimoxazole in chronic renal failure. Lancet 1: 1216–1218
Fabre J, Balant L (1976) Renal failure, drug pharmacokinetic and drug action. Clin. Pharmacokinet 1: 99–120
Patel RB, Welling PG (1980) Clinical Pharmacokinetics of co-trimoxazole (trimethoprim-sulphamethoxazole). Clin. Pharmacokinet 5: 405–423
Rubin RH, Schwartz MN (1980) Trimethoprim-Sulfamethoxazole. N Engl J Med 303: 426–432
Anton AM, Corey WT (1971) Plasma protein binding of sulfonamides in anephric patients. Fed Proc 30: 629–634
Gugler R, Azarnoff DL (1976) Drug protein binding and the nephrotic syndrome. Clin Pharmacokinet 1: 25–35
Koch Weser J, Sellers AM (1976) Binding of drug to serum albumin. N Engl J Med 294: 526–530
Reidenberg MM (1970) The binding of drugs to plasma proteins and the interpretation of measurements of plasma concentrations of drugs in patients with poor renal function. Am J Med 62: 466–470
Welling PG, Craig WA, Amidon GL, Kunin CM (1973) Pharmacokinetics of trimethoprim and sulfamethoxazole in normal subjects and in patients with renal failure. J Infect Dis 128: 556–566
Golper TA (1979) Drug and peritoneal dialysis. Dialysis Transplant 8: 41–44
Hoppe Seyler G, Schollmeyer P, Grandpierre B, Löffler HD (1975) The relationship between sulfamethoxazole and trimethoprim pharmacokinetics and disturbed excretion in the functionally anephric patients undergoing home and peritoneal dialysis. Proc. 6th Int. Congress of Pharmacology, Helsinki. abst 492: 192
Singlas E, Rottembourg J, de Martin A, Colin JN, Legrain M (1981) Pharmacokinetics of Co-trimoxazole using the peritoneal route. Consequence for the treatment of peritonitis in patients maintained on peritoneal dialysis. In: Moncrief JM (ed) Continuous ambulatory peritoneal dialysis. Int. Symposium II. Austin Excerpta Medica, Amsterdam
Kaplan SA, Weinfeld RE, Abruzzo CW, Macfaden K, Jack ML, Weissman L (1973) Pharmacokinetic profil of trimethoprim-sulfamethoxazole in man. J Infect Dis 128: 547–555
Rieder J (1973) Metabolism and techniques for assay of trimethoprim and sulfamethoxazole. J Infect Dis 128: 567–673
Schwartz DE, Vetter W, Englert G (1970) Trimethoprim metabolites in rat, dog and man: qualitative and quantitative studies. Arzneim Forsch 20: 1867–1871
Bohni E (1969) Vergleichende Untersuchungen mit der Kombination Trimethoprim/Sulfamethoxazol in vitro und in vivo. Chemotherapy 14: 1–21
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Singlas, E., Colin, J.N., Rottembourg, J. et al. Pharmacokinetics of sulfamethoxazole - trimethoprim combination during chronic peritoneal dialysis: Effect of peritonitis. Eur J Clin Pharmacol 21, 409–415 (1982). https://doi.org/10.1007/BF00542328
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00542328