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Pharmacokinetics of oral cephalosporins
902
Editorial correspondence
The Journal of Pediatrics November 1978
comparing the pharmacokinetic characteristics of cephradine and cephalexin in 1 and 2 gm doses. As can be seen from the Table, all measurements were essentially identical, and are not significantly different from those previously reported by Nightingale et al ~ and Finkelstein et al 3 at lower doses. Our conclusion is that, from a pharmacokinetic view, these agents are virtually identical. Our work confirms the suggestion of Tetzlaff et al 1 that the pharmacokinetics of cephalexin do not change as a function of dose. Although our work was performed in adults, .both cephalexin and cephradine, because of their molecular similarities, are handled in the same manner by the body, i.e., eliminated via renal excretion with insignificant metabolism and protein binding. The comparison of these drugs in adults should, therefore, also be valid in children. This is not to say that the doses in children and adults should be the same on a weight basis, but the pharmacokinetics of either drug in children should be the same and independent of dose.
at leptomeningeal sites, changing the rate of CSF production or reabsorption, and thus causing intracranial hypertension.
Bradley Hall Stuart, M.D. Department of Emergency Medicine Kaiser Foundation Medical Center Santa Clara, CA Iris F. Litt, M.D. Adolescent Medicine Stanford University Medical Center Stanford, CA 94305 REFERENCES 1. Drew TM, Altman R, and Black K, et al: Minocycline for prophylaxis of infection with Neisseria meningitidis: high rate of side-effects in recipients, J Infect Dis 133:194, 1976. 2. Singer I, and Rotenberg D: Demeclocycline-induced nephrogenic diabetes insipidus: in vivo and in vitro studies, Ann Intern Med 79:679, 1973. 3. Forrest JN, Cox M, and Hong C, et al: Demeclocycline versus lithium for inappropriate secretion of antidiuretic hormone, N Engl J Med 298:173, 1978.
Elaine R. Finkelstein, Pharm. D. School of Pharmacy State University of New York at Buffalo Amherst, N Y 14260 Richard Quintiliani, M.D. Hartford Hospital Hartford, CT Charles H. Nightingale, Ph.D. School of Pharmacy State University of New York at Buffalo Amherst, N Y 14260
Pharmacokinetics of oral cephalosporins To the Editor: Recen~dy, Tetztaff et alI published an article concerning the bioavailability of cephalexin in children. The authors suggested that the absorption characteristics and pharmacokinetics of cephalexin do not differ as a function of dose. We have studied the pharmacokinetics of both cephalexin and cephradine in high and low doses in adults, and found these drugs to be remarkably similar. Nightingale et al 2 concluded that these agents were virtually identical kinetically at 0.25 and 0.5/~m doses. This was confirmed in a crossover study comparing cephal~xin and cephradine in I gm doses using a multiple dose regimen? More recently, we have conducted crossover studies in five subjects
REFERENCES 1. Tetzlaff TR, McCracken GH, and Thomas ML: Bioavailability of cephalexin in children: Relationship to drug formulations and meals, J PEDIATR 92:292, 1978. 2. Nightingale CH, Greene DS, and Quintiliani R: Pharmacokinetics and clinical use of cephalosporin antibiotics, J Pharm Sci 64:1899, 1975. 3. Finkelstein E, Quintiliani R, Lee R, Bracci A, and Nightingale CH: Pharmacokinetics-of oral cephalosporins-cephradine and cephalexin, J Pharm Sci (in press).
Table
Pharmacokinetic measurement AUC (/tg-min/ml) Peak time (min) Peak time (/~g/ml) Lag time (min) tJh elim (min) tlA abs (min) Urinary recovery (%) Vd (1)
Cephradine (1 gm every 4 hr)
Cephradine (2 gm every 6 hr)
Cephalexin (1 gm every 4 hr)
Cephalexin (2 gm every 6 hr)
2,984.0 71.0 28.6 24.0 40.4 19.2 103:2 19.8
6,151.7 81.5 44.9 27.3 51.4 44.4 89.7 24.8
3,341.1 65.5 33.2 18.5 47.5 23.4 91.1 20.8
6,981.4 83.7 50.5 33.1 51.4 47.9 91.9 21.3
± 493.3 _+ 13.0 _ 1.7 _+ 11.9 _ 4.4 ___ 7.1 ± 9.0 + 2.4
_+ 798.4 _+ 22.7 - 10.1 --_ 20.1 + 8.7* _ 14.9' + 11.1 ± 7.4
± 553.8 ± 10.7 ± 6.1 ___ 5.9 ± 2.6 ± 8.4 ± 7.6 --_ 2.4
Student t tests were used to compare all pharmacokinetic measurements between drugs at the same dose and within drug groups. *P < 0.05. Cephradine: 1 gm vs 2 gm Tth elim and T ~habs. Cephalexin: 1 gm vs 2 gm lag time.
± 687.1 ± 18.3 _+ 4.0 ± 8.0* ± 5.5 _+ 26.1 _+ 6.6 _+ 1.6
Editorial correspondence
The Journal of Pediatrics November 1978
comparing the pharmacokinetic characteristics of cephradine and cephalexin in 1 and 2 gm doses. As can be seen from the Table, all measurements were essentially identical, and are not significantly different from those previously reported by Nightingale et al ~ and Finkelstein et al 3 at lower doses. Our conclusion is that, from a pharmacokinetic view, these agents are virtually identical. Our work confirms the suggestion of Tetzlaff et al 1 that the pharmacokinetics of cephalexin do not change as a function of dose. Although our work was performed in adults, .both cephalexin and cephradine, because of their molecular similarities, are handled in the same manner by the body, i.e., eliminated via renal excretion with insignificant metabolism and protein binding. The comparison of these drugs in adults should, therefore, also be valid in children. This is not to say that the doses in children and adults should be the same on a weight basis, but the pharmacokinetics of either drug in children should be the same and independent of dose.
at leptomeningeal sites, changing the rate of CSF production or reabsorption, and thus causing intracranial hypertension.
Bradley Hall Stuart, M.D. Department of Emergency Medicine Kaiser Foundation Medical Center Santa Clara, CA Iris F. Litt, M.D. Adolescent Medicine Stanford University Medical Center Stanford, CA 94305 REFERENCES 1. Drew TM, Altman R, and Black K, et al: Minocycline for prophylaxis of infection with Neisseria meningitidis: high rate of side-effects in recipients, J Infect Dis 133:194, 1976. 2. Singer I, and Rotenberg D: Demeclocycline-induced nephrogenic diabetes insipidus: in vivo and in vitro studies, Ann Intern Med 79:679, 1973. 3. Forrest JN, Cox M, and Hong C, et al: Demeclocycline versus lithium for inappropriate secretion of antidiuretic hormone, N Engl J Med 298:173, 1978.
Elaine R. Finkelstein, Pharm. D. School of Pharmacy State University of New York at Buffalo Amherst, N Y 14260 Richard Quintiliani, M.D. Hartford Hospital Hartford, CT Charles H. Nightingale, Ph.D. School of Pharmacy State University of New York at Buffalo Amherst, N Y 14260
Pharmacokinetics of oral cephalosporins To the Editor: Recen~dy, Tetztaff et alI published an article concerning the bioavailability of cephalexin in children. The authors suggested that the absorption characteristics and pharmacokinetics of cephalexin do not differ as a function of dose. We have studied the pharmacokinetics of both cephalexin and cephradine in high and low doses in adults, and found these drugs to be remarkably similar. Nightingale et al 2 concluded that these agents were virtually identical kinetically at 0.25 and 0.5/~m doses. This was confirmed in a crossover study comparing cephal~xin and cephradine in I gm doses using a multiple dose regimen? More recently, we have conducted crossover studies in five subjects
REFERENCES 1. Tetzlaff TR, McCracken GH, and Thomas ML: Bioavailability of cephalexin in children: Relationship to drug formulations and meals, J PEDIATR 92:292, 1978. 2. Nightingale CH, Greene DS, and Quintiliani R: Pharmacokinetics and clinical use of cephalosporin antibiotics, J Pharm Sci 64:1899, 1975. 3. Finkelstein E, Quintiliani R, Lee R, Bracci A, and Nightingale CH: Pharmacokinetics-of oral cephalosporins-cephradine and cephalexin, J Pharm Sci (in press).
Table
Pharmacokinetic measurement AUC (/tg-min/ml) Peak time (min) Peak time (/~g/ml) Lag time (min) tJh elim (min) tlA abs (min) Urinary recovery (%) Vd (1)
Cephradine (1 gm every 4 hr)
Cephradine (2 gm every 6 hr)
Cephalexin (1 gm every 4 hr)
Cephalexin (2 gm every 6 hr)
2,984.0 71.0 28.6 24.0 40.4 19.2 103:2 19.8
6,151.7 81.5 44.9 27.3 51.4 44.4 89.7 24.8
3,341.1 65.5 33.2 18.5 47.5 23.4 91.1 20.8
6,981.4 83.7 50.5 33.1 51.4 47.9 91.9 21.3
± 493.3 _+ 13.0 _ 1.7 _+ 11.9 _ 4.4 ___ 7.1 ± 9.0 + 2.4
_+ 798.4 _+ 22.7 - 10.1 --_ 20.1 + 8.7* _ 14.9' + 11.1 ± 7.4
± 553.8 ± 10.7 ± 6.1 ___ 5.9 ± 2.6 ± 8.4 ± 7.6 --_ 2.4
Student t tests were used to compare all pharmacokinetic measurements between drugs at the same dose and within drug groups. *P < 0.05. Cephradine: 1 gm vs 2 gm Tth elim and T ~habs. Cephalexin: 1 gm vs 2 gm lag time.
± 687.1 ± 18.3 _+ 4.0 ± 8.0* ± 5.5 _+ 26.1 _+ 6.6 _+ 1.6