Summary
The pharmacokinetics and metabolism of cimetidine were studied in five cystic fibrosis patients (mean age 12.6 years) after oral and intravenous administration. As compared to healthy adult volunteers, cystic fibrosis children had an elevated cimetidine total body clearance (474 vs 300 ml/min/m2) as well as renal clearance (293 vs 232 ml/min/m2) whether normalized for body weight or surface area differences. Cimetidine elimination was elevated in juvenile cystic fibrosis patients as compared to adult volunteers, however, it did not differ significantly from that previously seen in age matched children. There were no appreciable differences in cimetidine metabolism after either route of administration. Differences between adults and cystic fibrosis children were attributed to developmental and age related differences between the two groups. The recommended pediatric dose of 15 to 20 mg/kg, although four-fold greater than that used in adults, produces serum concentrations similar to those seen in adults, and is adequate for most juvenile cystic fibrosis patients.
Similar content being viewed by others
References
Heizer WD, Cleaveland CR, Iber FL (1965) Gastric inactivation of pancreatic supplements. Bull Johns Hopkins Hosp 116: 262–270
Cox KL, Isenberg JN, Osher AB, Dooley RR (1979) The effects of cimetidine on maldigestion in cystic fibrosis. J Pediatr 94: 488–492
Durie PR, Bell L, Linton W, Corey ML, Forstner GG (1980) Effect of cimetidine and sodium bicarbonate on pancreatic replacement therapy in cystic fibrosis. Gut 21: 778–786
Regan PT, Malagelada JR, DiMagno EP, Olanzman SL, Go VL (1977) Comparative effects of antacids, cimetidine and enteric coating on the therapeutic response to oral enzymes in severe pancreatic insufficiency. N Engl J Med 297: 854–858
Somogyi A, Gugler R (1982) Drug interactions with cimetidine. Clin Pharmacokinet 7: 23–41
Ufberg MG, Brooke CM, Bosanac PR et al. (1977) Transient neutropenia in a patient receiving cimetidine. Gastroenterol 73: 635–638
Chang KH, Morrison MD (1979) Bone marrow suppression with cimetidine. Ann Intern Med 91: 580
Lilly JR, Hitch DC, Javitt NB (1978) Cimetidine cholestatic jaundice in children. J Surg Res 24: 384–387
Bradbear RA, Shepherd RW, McGuffie C, Grice J, Roberts RK (1981) The kinetics of oral cimetidine in children with cystic fibrosis. Br J Clin Pharmacol 12: 248–249
Ziemniak JA, Chiarmonte DA, Schentag JJ (1981) Liquidchromatographic determination of cimetidine, its known metabolites and creatinine in serum and urine. Clin Chem 27: 272–275
Jusko WJ (1980) Guidelines for collection and pharmacokinetic analysis of drug disposition data. In: Evans WE, Schentag JJ, Jusko WJ (eds) Applied pharmacokinetics. Applied Therapeutics Inc., San Francisco, California, pp 639–680
Walkenstein SS, Dubb JW, Randolph WC, Westlake WJ, Stote RM, Intoccia AP (1978) Bioavailability of cimetidine in man. Gastroenterology 74: 360–366
Somogyi A, Rhonei HG, Gulger R (1980) Pharmacokinetics and bioavailability of cimetidine in gastric and duodenal patients. Clin Pharmacokinet 5: 84–94
Shwachman H, Dooley RR, Guilmette F, Patterson PR, Weil C, Leubner H (1956) Cystic fibrosis of the pancreas with varying degrees of pancreatic insufficiency. Am J Dis Child 92: 347–368
Park RW, Grand RJ (1981) Gastrointestinal manifestations of cystic fibrosis: A review. Gastroenterology 81: 1143–1161
Lowe CU, Buck E, Mosovich LL (1972) Cystic fibrosis of the pancreas. In: Barnett HL, Einhorn AH (eds) Pediatrics, Appleton-Century-Crofts, New York NY, pp 413–430
Jusko WJ, Mosovich LL, Gerbracht LM, Mattai ME, Yaffe SJ (1977) Enhanced renal excretion of dicloxacillin in patients with cystic fibrosis. Pediatrics 56: 1038–1044
Yaffe SJ, Gerbracht LM, Mattai ME, Danish M, Jusko WJ (1977) Pharmacokinetics of methicillin in patients with cystic fibrosis. J Infect Dis 135: 828–831
Kelly HB, Mendez R, Fan L, Murphy S (1982) Pharmacokinetics of tobramycin in cystics fibrosis. J Pediatr 100: 318–321
Kearns GL, Hilman B, Wilson JT (1982) Dosing implications of altered gentamicin disposition in patients with cystic fibrosis. J Pediatr 100: 312–318
Bertrand MC, DeBievelle F, Neijens H et al. (1982) Trace metals in cystic fibrosis. Acta Pediatr Scand: 71: 203–207
Spino M, Chai R, Isles AF (1983) Renal function in cystic fibrosis. Clin Pharmacol Ther 33: 244
Chin TW et al. (1983) Pharmacokinetics of cimetidine in critically ill children. Pediatr Pharmacol 2: 285
Taylor D, Cresswell PR, Bartlet DC (1978) The metabolism and elimination of cimetidine, a histamine H2-receptor antagonist in the rat, dog and man. Drug Metab Disp 6: 21–29. L 1978
Larsson R, Erlanson P, Bodemar G et al. (1982) The pharmacokinetics of cimetidine and its sulfoxide metabolite in patients with normal and impaired renal function. Br J Clin Pharmacol 13: 164–170
Bodemar G, Norlander B, Fransson L, Walan A (1979) The absorption of cimetidine and the influence of a meal on the absorption of cimetidine. Studies in patients with peptic ulcer disease. J Clin Pharmacol 7: 23–31
Grahnen A, Bahr C, Lindstrom B, Rosen A (1979) Bioavailability and pharmacokinetics of cimetidine. Eur J Clin Pharmacol 16: 335–340
Pedersen PV, Miller R (1980) Pharmacokinetics and bioavailability of cimetidine in humans. J Pharm Sci 69: 394–398
Gulger R, Somogyi A, Bergman K (1981) The biliary excretion of histamine H2-receptor antagonists cimetidine and oxmetidine. Clin Pharmacol Ther 29: 249
Spence RW, Celestin LR, DeLaGuardia R et al. (1977) Biliary secretion of cimetidine in man. In: Burland WL, Simkins MA (eds) Proceedings of the Second International Symposium on Histamine H2-receptor antagonists. Excerpta Medica, Amsterdam, pp 81–86
VanHecken AM, Tjandramaga TB, Mullie A et al. (1980) Ranitidine: Single dose pharmacokinetics and absolute bioavailability in man. Br J Clin Pharmacol 14: 195–200
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ziemniak, J.A., Assael, B.M., Padoan, R. et al. The bioavailability and pharmacokinetics of cimetidine and its metabolites in juvenile cystic fibrosis patients: Age related differences as compared to adults. Eur J Clin Pharmacol 26, 183–189 (1984). https://doi.org/10.1007/BF00630284
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00630284