Summary
In the present study, ribostamycin concentrations in serum were measured by microbiological assay in 20 paediatric patients aged 3 months to 11 years after intramuscular ribostamycin 10, 15 and 20 mg/kg. All pharmacokinetic parameters and statistical analyses were calculated by computer. These results showed that the absorption rate constant (ka), elimination rate constant (ke), time to peak serum concentration (tmax), elimination half-life (t½), apparent volume of distribution (Vd/F), total body clearance (CL) and area under the serum concentration-time curve (AUC) were significantly different in infants under 6 months from those in children over 3 years (p < 0.05), except for the peak serum concentration (Cmax) and lag time from administration to the first appearance of drug in the serum (tlag) [p > 0.05]. The absorption of ribostamycin in infants was more rapid than that in children, but elimination was slower (p < 0.05). The Vd/F and CL in infants were also larger than in children (p < 0.01). There were significant positive correlations between Cmax, AUC and ribostamycin dosage (p < 0.01). Pharmacokinetic parameters for infants and children were compared with those observed in adults, and it was found that ribostamycin absorption and elimination were more rapid in the paediatric patients. The Cmax in children and infants after intramuscular ribostamycin 10 mg/kg approached that in adults after an intramuscular dose of ribostamycin 500mg. Using a 1-compartment open pharmacokinetic model, the optimum intramuscular ribostamycin administration interval was estimated as 6.01 and 7.56h for children and infants, respectively, while the value was 8.5h in adults. When the drug was administered in multiple doses of 15 mg/kg intramuscularly every 8h, no accumulation occurred in children. It is suggested that ribostamycin be administered in intramuscular doses of 10 to 15 mg/kg twice daily in infants and 3 times daily in children, respectively.
Similar content being viewed by others
References
Di Nola F, Eandi M, Soranzo ML. Kinetic and clinical research into a new aminoglycosidic antibiotic: ribostamycin. Drugs Under Experimental and Clinical Research 6: 77–90, 1980
Evans EF, Proctor JD, Fratkin MJ, Velandia J, Wasserman AJ. Blood flow in muscle groups and drug absorption. Clinical Pharmacology and Therapeutics 17: 44–47, 1975
Hayton WL, Stoeckel K. Age-associated changes in ceftraxone pharmacokinetics. Clinical Pharmacokinetics 11: 76–86, 1986
Inouye S, Watanabe T, Kitasato I. Comparative antimicrobial activities of ribostamycin, gentamicin, ampicillin and lincomycin in vitro and in vivo. Drugs Under Experimental and Clinical Research 15: 465–476, 1989
Kasik JW, Jenkins S, Lenschen MP, Nelson RM. Postconceptional age and gentamicin elimination half-life. Journal of Pediatrics 106: 502–505, 1985
Kearns GL, Reed MD. Clinical pharmacokinetics in infants and children: a reappraisal. Clinical Pharmacokinetics 17 (Suppl. 1): 29–67, 1989
Kelman AW, Thomson AH, Whiting B, Bryson SM, Steedman DA, et al. Estimation of gentamicin clearance and volume of distribution in neonates and young children. British Journal of Clinical Pharmacology 18: 685–692, 1984
Kitasato I, Niizato T, Inouye S. Comparative nephrotoxicity of ribostamycin and gentamicin in rats evaluated by urinalysis. Drugs Under Experimental and Clinical Research 15: 273–289, 1989
Lechi A, Arosio E, Rizzotti P, et al. Comparative effects of gentamycin and ribostamycin therapy of urinary infections on two enzymatic markers of tubular function. Drugs Under Experimental and Clinical Research 8: 517–524, 1982
Liu Y-h, Dai X-m, et al. Pharmacokinetics of ribostamycin in healthy volunteers. Chinese Journal of Antibiotics 9: 491–494, 1984
Morselli PL, Franco-Morselli R, Bossi L. Clinical pharmacokinetics in newborns and infants: age-related differences and therapeutic implications. Clinical Pharmacokinetics 5: 485–527, 1980
Morselli PL, Thiercelin JF. Human neonatal pharmacokinetics. In Turner & Shand (Eds) Recent advances in clinical pharmacology, pp. 21–43, Churchill Livingstone Publishers, London, 1983
Nakazawa S, Dka S, Sato H, Imai S, Mochizuki Y, et al. Laboratory and clinical studies on a new antibiotic, ribostamycin Meiji (Vistamycin, VSM) in the field of pediatrics. Chemotherapy 20: 94–99, 1972
Niems AH. Renal elimination of drugs at various ages. In Turner (Ed.) Clinical pharmacology and therapeutics, pp. 117–123, Macmillan, London, 1980
Renna G, Siro-Brigiani G, Cuomo V. Comparative evaluation of the neuromuscular blocking activity of three new aminoglycoside antibiotics in rats. Toxicology Letter 9: 107–112, 1981
Reynolds JEF. Martindale: the extra pharmacopoeia, 28th ed., pp. 1208, Pharmaceutical Press, London, 1982
Saito H, Inoue Y, Date K, Yasuno T, Mizukoshi O. Ototoxicity of vistamycin. Chemotherapy 20: 243–248, 1972
Sato K, Saito T, Matsuhira T. Comparative study by scanning electron microscopy on vestibular toxicities of dibekacin, ribostamycin and other aminoglycoside antibiotics in guinea pigs. International Journal of Clinical Pharmacology Therapy and Toxicology 12: 109–114, 1983
Wu L-W. Therapeutic drug monitoring, p. 400, People’s Health Publishing Company, Beijing, 1989
Yamasaku F, Suzuki Y, Umenura K. Pharmacokinetics of ribostamycin in healthy volunteers and patients with impaired renal function. Japanese Journal of Antibiotics 33: 1318–1331, 1980
Yang Y-c, Chen G, Yuan L. A non-linear method and its program for calculating pharmacokinetic parameters. Acta Pharmacologica Sinica 4: 217–220, 1983
Zhang M-f, Gu Y-m, et al. Studies on the clinical pharmacology of ribostamycin. New Drugs Clinical Remedies 4: 199–201, 1985
Zhou S-l, Zhong H-f, Shen G, Zhang A-z, et al. The stability of ribostamycin sulfate in phosphate buffer solution and three infusion solutions. Chinese Pharmaceutical Journal 25: 589–592, 1990
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zhou, Sl., Shen, G. & Zhong, Hf. Pharmacokinetics of Ribostamycin in Paediatric Patients. Clin. Pharmacokinet. 22, 144–151 (1992). https://doi.org/10.2165/00003088-199222020-00005
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-199222020-00005