Summary
The interaction between a new macrolide antibiotic, miocamycin, and theophylline was evaluated in a single cross-over study in 5 asthmatic children. Each patient received a single dose of theophylline (4.3 mg/kg) delivered in 15 min using a constant-rate infusion pump, immediately before and after a 10 day course of miocamycin 17.5 mg/kg b.d. The pharmacokinetics of theophylline were calculated for each phase of the study. The elimination rate constant (3.92 vs 3.74 h−1), the mean total body clearance (1.71 vs 1.8 ml·min·kg−1) and the mean apparent volume of distribution (0.57 vs 0.58 l·kg−1) did not differ. The result can be explained by the inability of the antibiotic to form inactive cytochrome P-450 metabolite complexes which can interfere with the metabolism of theophylline. Thus, miocamycin can safely be administered to asthmatic children requiring theophylline treatment, when they have an infection due to susceptible pathogens.
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References
Long SS (1983) Treatment of acute pneumonia in infants and children. Ped Clin N Am 30: 297–321
Henderson FW, Clyde WA, Collier AM, Denny FW, Senior RJ, Sheaffer CI, Conley WG, Christian RM (1979) The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice. J Pediatr 95: 183–190
Weinberger M, Hudgel D, Spector S, Chidsey C (1977) Inhibition of theophylline clearance by troleandomycin. J Allergy Clin Immunol 11: 228–231
Brazier JL, Kofman J, Faucon G, Perrin-Fayolle M, Lepape A, Lanoue R (1980) Retard d'elimination de la theophylline dû à la troleandomycin. Absence d'effect de la josamycin. Thérapie 35: 545–548
Parrish RA, Haulman J, Burns RM (1983) Interaction of theophylline with erythromycin base in a patient withseizure activity. Pediatrics 72: 828–830
Zarowitz BJM, Szefler SJ, Lasezkay GM (1981) Effect of erythromycin base on theophylline kinetics. Clin Pharmacol Ther 29: 601–605
Kozak PP Jr, Cummins LH, Gillman SA (1977) Administration of erythromycin to patients on theophylline. J Allergy Clin Immunol 60: 149–151
Cummins LH, Kozak PP Jr, Gillman SA (1977) Erythromycin's effect on theophylline blood levels. Pediatrics 59: 144
Fucaya K, Shomura T, Someya S, Kitai S, Murata S, Umemura K (1981) Absorption, metabolism and excretion of 9.34 diacetylmidecamycin (MOM) in human. Acta Toxicol Ther 2: 45–64
Gismondo MR, Romeo MA, Tempera G, Iannello D, Carbone M (1983) Comparative effects of subinhibitory concentrations of miocamycin and other antibiotics on oral Streptococci. Drugs Exp Clin Res 11: 801–808
Olivi O (1985) Efficacy and tolerance of miocamycin, a new macrolide, in paediatrics. Proceedings of the 14th International Congress of Chemotherapy, Kioto, Japan. Abstract S-35-9
Alesina R, Colombo ML, Ferrara A, Gialdroni Grassi G (1981) Attività antibatterica in vitro della miocamicina. Chemioter Antimicrobica 4: 341–350
Loughnan PM, Sitar DS, Ogilvie RI, Eisen A, Fow Z, Neims AM (1976) Pharmacokinetic analysis of the disposition of intravenous theophylline in young children. J Pediatr 88: 874–879
Gibaldi M, Perrier D (1975) Pharmacokinetics. Marcel Dekker, New York, p 69
Snedecor GW, Cochran WG (1967) The comparison of two samples. In: Statistical methods. Ames, Iowa State University Press- pp 91–104
Ellis EF, Koyssoko R, Levy G (1976) Pharmacokinetics of theophylline in children with asthma. Pediatrics 58: 542–547
Pfeifer HJ, Greenblatt DJ, Friedman P (1979) Effects of three antibiotics on theophylline kinetics. Clin Pharmacol Ther 26: 36–40
Hildebrandt R, Gundert-Remy U, Moller H, Weber E (1984) Lack of clinically important interaction between erythromycin and theophylline. Eur J Clin Pharmacol 26: 485–489
Renton KW, Gray JD, Hung OR (1981) Depression of theophylline elimination by erythromycin. Clin Pharmacol Ther 30: 422–426
Prince RA, Wings DS, Weinberger MM, Hendeles LS, Riegelman S (1981) The effect of erythromycin on theophylline kinetics. J Allergy Clin Immunol 68: 427–431
Pessayre D, Descatore V, Konstantinova-Mitcheva M, Wandscheer JC, Cobert B, Level R, Benhamou JP, Jaouen M, Mansuy D (1981) Self-induction by triacetyloleandomycin of its own transformation into a metabolite forming a stable 456 nmabsorbing complex with cytochrome P-450. Biochem Pharmacol 30: 553–558
Pessayre D, Konstantinova-Mitcheva M, Descatoire V, Cobert B, Wandscheer JC, Level R, Feldmann G, Mansuy D, Benhamou JP (1981) Hypoactivity of cytochrome P-450 after triacetyloleandomycin administration. Biochem Pharmacol 30: 559–564
Pessayre D, Descatoire V, Tinel M, Larrey D (1982) Self-induction by oleandomycin of its own transformation into a metabolite forming an inactive complex with reduced cytochrome P-450. Comparison with troleandomycin. J Pharmacol Exp Ther 221: 211–221
Danan G, Descatoire V, Pessayre D (1981) Self-induction by erythromycin of its own transformation into a metabolite forming an inactive complex with reduced cytochrome P-450. J Pharmacol Exp Ther 218: 509–514
Hendeles L, Weinberger M (1983) Theophylline. In: Ellis E, Reed C (eds) Allergy: Principles and Practice. T CV Mosby, Scan Louis, pp 535–574
Ruff F, Santais MC, Chastagnol D, Huchon G, Durieux P (1981) Macrolide et theophylline: Absence d'interaction josamycine-theophylline. Nouv Presse Med 10: 175
Lavarenne J, Paire M, Talon O (1981) Influence d'un nouveau macrolide, la midecamycine, sur les taux sangiuns de theophylline. Thérapie 36: 451–456
Larrey D, Tinel M, Pessayre D (1983) Formation of inactive cytochrome P-450 Fe(II)-metabolite complexes with several erythromycin derivatives but not with josamycin and midecamycin in rats. Biochem Pharmacol 32: 1487–1493
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Principi, N., Onorato, J., Giuliani, M.G. et al. Effect of miocamycin on theophylline kinetics in children. Eur J Clin Pharmacol 31, 701–704 (1987). https://doi.org/10.1007/BF00541298
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DOI: https://doi.org/10.1007/BF00541298