Summary
The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal fluid concentrations and safety of intravenous rifampin in pediatric patients undergoing shunt placement. Nine patients (mean age 5.6 y) received a single dose of rifampin, 20 mg · kg−1, administered intravenously 1 h prior to surgery.
The peak serum concentrations ranged from 13.5–26.7 μg · ml−1; cerebrospinal fluid concentrations ranged from 0.12–3.0 (mean: 1.4) μg · ml−1. The mean total clearance, apparent distribution volume, and elimination half-life were 0.291 · kg−1 · h−1, 1.11 · kg−1, and 2.8 h. The concentrations of rifampin achieved in the cerebrospinal fluid exceeded the minimum inhibitory concentrations by 100-to 1000-fold against Staphylococcus epidermidis.
However, 5 of 9 patients developed cutaneous reactions during intravenous rifampin prophylactic therapy. Because of the high frequency of adverse effects and more than adequate rifampin concentrations achieved in the cerebrospinal fluid, rifampin doses lower than that used in this study may be evaluated in future studies.
Similar content being viewed by others
References
Schoenbaum SC, Gardner P, Schillito J (1975) Infections of cerebrospinal fluid shunts: epidemiology, clinical manifestations and therapy. J Infect Dis 131: 543–552
George R, Leibrock L, Epstein M (1979) Long term analysis of cerebrospinal fluid shunt infections. A 25 year experience. J Neurosurg 51: 804–811
Thornsberry C, Hill BC, Swenson JM, McDougal LK (1983) Rifampin: spectrum of antibacterial activity. Rev Inf Dis 5 [Suppl 3]: S412-S417
Koup JR, Williams-Warren J, Viswanathan CT, et al. (1986) Pharmacokinetics of rifampin in children, II. Oral bioavailability. Ther Drug Monit 8: 17–22
Sippel JE, Mikhail IA, Girgis NI, Youssef HH (1974) Rifampin concentrations in cerebrospinal fluid of patients with tuberculosis meningitis. Am Rev Respir Dis 109: 579–580
Weber A, Opheim KE, Smith AL, Wong K (1983) High pressure liquid chromatographic quantitation of rifampin and its two major metabolites in urine and serum. Rev Inf Dis 5 [Suppl 3]: S433-S439
Ratti B, Parenti R, Toselli A, Zerilli LF (1981) Quantitative assay of rifampicin and its main metabolite 25-desacetylrifampicin in human plasma by reversed phase high performance liquid chromatography. J Chromatogr 225: 526–531
Fan-Harvard P, Nahata MC, Barsm WJ, Bartkowski H, Kosnik E (1988) Histamine-like reaction after a single intravenous dose of rifampin. Clin Pharm 7: 616–620
Garrelts JC, Petcrie JD (1985) Vancomycin and the “red man's syndrome.” N Engl J Med 312: 245
D'Oliveira JJ (1972) Cerebrospinal fluid concentrations of rifampin in meningeal tuberculosis. Am Rev Resp Dis 106: 432–436
Koup JR, Williams-Warren J, Viswanathan CT, Weber A, Smith AL (1986) Pharmacokinetics of rifampin in children, I. multiple dose intravenous infusion. Ther Drug Monit 8: 11–16
Author information
Authors and Affiliations
Additional information
Supported by grants from the Children's Hospital Research Foundation, and Ohio State University office of Health Services
Rights and permissions
About this article
Cite this article
Nahata, M.C., Fan-Havard, P., Barson, W.J. et al. Pharmacokinetics, cerebrospinal fluid concentration, and safety of intravenous rifampin in pediatric patients undergoing shunt placements. Eur J Clin Pharmacol 38, 515–517 (1990). https://doi.org/10.1007/BF02336694
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02336694