Skip to main content
SpringerLink
Log in

Clinical Pharmacokinetics in Infants and Children

  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Wide variations in drug dose recommendations for children of the same or different ages reflect the inadequacy of data on pharmacokinetics and pharmacodynamics in children. Selected aspects of available literature on pharmacokinetics of drugs used in older infants and children has been reviewed with special attention to calculation of an age-appropriate dose.

During the neonatal period and early infancy the elimination of many drugs that are excreted in the urine in unchanged form is restricted by the immaturity of glomerular filtration and renal tubular secretion. On the other hand, in late infancy and/or in childhood, a similar or greater rate of elimination from plasma than in adults has been observed for many drugs, notably digoxin, phenobarbitone, phenytoin, carbamazepine, ethosuximide, diazoxide, clindamycin and propoxyphene. Consistent with this, it has been shown that some drugs exhibit a lower plasma level/dose ratio in infancy and early childhood as compared with the adult. This is true for phenobarbitone, phenytoin and ethosuximide.

Some age groups of children remain uninvestigated with regard to pharmacokinetics, even for the drugs reviewed. Therefore, pediatric therapy remains empirically based for many drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Altman, P.L. and Dittmer, D.S.: Biological Handbooks, Growth, Federation of American Societies of Experimental Biology, Washington, DC, p.337–347 (1962).

  • Arnold, K. and Gerber, N.: The rate of decline of diphenylhydantoin in human plasma. Clinical Pharmacology and Therapeutics 11: 121 (1970).

    PubMed  CAS  Google Scholar 

  • Axline, S.G.; Yaffe, S.J. and Simon, H.J.: Clinical pharmacology of antimicrobials in premature infants. Pediatrics 39: 97–107 (1967).

    PubMed  CAS  Google Scholar 

  • Barnett, H.L.; McNamara, H.; Schultz, S. and Tompsett, R.: Renal clearances of sodium penicillin G, procaine penicillin G, and insulin in infants and children. Pediatrics 3: 418–422 (1949).

    PubMed  CAS  Google Scholar 

  • Becker, M.H.; Drachmen, R.H. and Kirscht, J.P.: Predicting mothers’ compliance with pediatric medical regimens. Journals of Pediatrics 81: 843–854 (1972).

    Article  CAS  Google Scholar 

  • Boerth, R.C.: Decreased sensitivity of newborn myocardium to the positive inotropic effects of ouabain; in Morselli, Garattini and Sereni (Eds) Basic and Therapeutic Aspects of Perinatal Pharmacology, p. 191–199 (Raven Press, New York 1975).

    Google Scholar 

  • Borofsky, L.G.; Louis, S.; Kutt, H. and Roginsky, M.: Diphenylhydantoin: Efficacy, toxicity and dose-serum level relationships in children. Journal of Pediatrics 81:995–1002 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Buchanan, R.A.; Fernandez, L. and Kinkel, A.W.: Absorption and elimination of ethosuximide in children. Journal of Clinical Pharmacology 9: 393–398 (1969).

    CAS  Google Scholar 

  • Buchthal, F. and Lennox-Buchthal, M.A.: Phenobarbital: Relation of serum concentration to control of seizures; in Woodbury, Penry and Schmidt (Eds) Antiepileptic Drugs, p. 335–343 (Raven Press, New York 1972).

    Google Scholar 

  • Buchthal, F.; Svensmark, O. and Schiller, P.J.: Clinical and electroencephalographic correlation with serum levels of diphenylhydantoin. Archives of Neurology 2: 624–630(1960).

    Article  PubMed  CAS  Google Scholar 

  • Butler, T.C.; Mahaffee, C. and Waddell, W.J.: Phenobarbital: Studies on elimination, accumulation, tolerance and dosage schedules. Journal of Pharmacology and Experimental Therapeutics 111: 425–435(1954).

    PubMed  CAS  Google Scholar 

  • Chang, T.; Dill, W.A. and Glazko, A.J.: Ethosuximide, Absorption, Distribution, and Excretion; in Woodbury, Penry and Schmidt (Eds) Antiepileptic Drugs, p.417–423 (Raven Press, New York 1972).

    Google Scholar 

  • Christiansen, J. and Dam, M.: Influence of phenobarbital and diphenylhydantoin on plasma carbamazepine levels in patients with epilepsy. Acta Neurologica Scandinavica 49: 543–546 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Conney, A.H.: Pharmacological implications of microsomal enzyme induction. Pharmacological Reviews 19: 317–366 (1967).

    PubMed  CAS  Google Scholar 

  • Doherty, J.E.; Hall, W.H.; Murphy, M.L. and Beard, O.W.: New information regarding digitalis metabolism. Chest 59: 433–437 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Doherty, J.E. and Perkins, W.H.: Studies with tritiated digoxin in human subjects after intravenous administration. American Heart Journal 63: 528–536 (1962).

    Article  PubMed  CAS  Google Scholar 

  • Dungan, W.T.; Doherty, J.E.; Harvey, C.; Char, F. and Dalrymple, G.V.: Tritiated digoxin: XVIII. Studies in infants and children. Circulation 46: 983–988 (1972).

    CAS  Google Scholar 

  • Eichelbaum, M. and Bertilsson, L.: Determination of carbamazepine and its epoxide metabolite in plasma by high speed liquid chromatography. Journal of Chromatography 103: 135–140(1975).

    Article  PubMed  CAS  Google Scholar 

  • Eichelbaum, M.; Bertilsson, L.; Lund, L.; Palmer, L. and Sjöqvist, F.: Plasma levels of carbamazepine and carbamazepine-10, 11-epoxide during carbamazepine therapy in epileptic patients. European Journal of Clinical Pharmacology. In press (1975).

  • Eichelbaum, M.; Bertilsson, L.; Rane, A. and Sjöqvist, F.: Autoinduction of carbamazepine metabolism in man. In manuscript (1975b).

  • Eichelbaum, M.; Ekbom, K.; Bertilsson, L.; Ringberger, V.A. and Rane, A.: Plasma kinetics of carbamazepine and its epoxide metabolite in man during single and multiple dosing. European Journal of Clinical Pharmacology 8: 337–341 (1975a).

    Article  PubMed  CAS  Google Scholar 

  • Ellis,E.F.; Koysooko, R. and Levy, G.: Pharmacokinetics of theophylline in children with asthma. In manuscript (1975).

  • Ellis, E.F.; Yaffe, S.J. and Levy, G.: 30th Annual Meeting (abstr.) of American Academy of Allergy, p.14 (1974).

  • Faerø, O.; Kastrup, K.W.; Lykkegaard Nielsen, E.; Melchior, J.C. and Thorn, J.: Successful Prophylaxis of Febrile Convulsions with Phenobarbital. Epilepsia 13: 279–285 (1972).

    Article  PubMed  Google Scholar 

  • Faigle, J.W.; Brechbühler, S. and Feldman, K.F.: The Biotransformation of Carbamazepine (Tegretol®); in Birk-mayer (Ed) Epileptic Seizures, Behaviour, Pain. In press (Verlag Hans Huber, Berne 1975).

    Google Scholar 

  • Fredholm, B.B.; Rane, A. and Persson, B.: Diphenylhydantoin binding to proteins in plasma and its dependence on free fatty acid and bilirubin concentration in dogs and newborn infants. Pediatric Research 9: 26–30(1975).

    Article  CAS  Google Scholar 

  • Frigerio, A.; Fanelli, R.; Biandrate, P.; Passerini, G.; Morselli, P.L. and Garattini, S.: Mass spectrometric characterization of carbamazepine-10,11-epoxide, a carbamazepine metabolite isolated from human urine. Journal of Pharmaceutical Sciences 61: 1144–1147 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Friis-Hansen, B.: Body water compartments in children: Changes during growth and related changes in body composition. Pediatrics 28: 169–181 (1961).

    PubMed  CAS  Google Scholar 

  • Garrettson, L.K. and Dayton, P.G.: Disappearance of phenobarbital and diphenylhydantoin from serum of children. Clinical Pharmacology and Therapeutics 11: 674–679 (1970).

    PubMed  CAS  Google Scholar 

  • Garrettson, L.K. and Jusko, W.J.: Diphenylhydantoin kinetics in overdosed children. Clinical Pharmacology and Therapeutics 17: 481–491 (1975).

    PubMed  CAS  Google Scholar 

  • Garrettson, L.K. and Kim, O.K.: Apparent saturation of diphenylhydantoin metabolism in children. Pediatric Research 4: 455 (1970).

    Article  Google Scholar 

  • Gibaldi, M.; Boyes, R.N. and Feldman, S.: Influence of first-pass effect on availability of drugs on oral administration. Journal of Pharmaceutical Science 60: 1338–1340(1971).

    Article  CAS  Google Scholar 

  • Goldblatt, E.: The treatment of cardiac failure in infancy. Lancet 2: 212–215 (1962).

    Article  PubMed  CAS  Google Scholar 

  • Goodman, L.S. and Gilman, A.: The Pharmacological Basis of Therapeutics, 5th ed. (Macmillan, New York 1975).

    Google Scholar 

  • Gorodischer, R.; Jusko, W.J. and Yaffe, S.J.: Renal clearance of digoxin in young infants. Pediatric Research. In press (1975a).

  • Gorodischer, R.; Jusko, W.J. and Yaffe, S.J.: Tissue and erythrocyte distribution of digoxin in infants. Journal of Pediatrics. In press (1975b).

  • Hernandez, A.; Burton, R.M.; Pagtakhan. R.D. and Goldring. D.; Pharmacodynamics of 3H-digoxin in infants. Pediatrics 44: 418–428 (1969).

    PubMed  CAS  Google Scholar 

  • Hoppel, C.; Garle, M.; Rane, A. and Sjöqvist, F.: Plasma concentrations of 5-(p-hydroxyphenyl)-5-phenyl-hydantoin in diphenylhydantoin treated patients. In manuscript (1976).

  • Hoppel, C.; Rane, A.; and Sjöqvist, F.: Kinetics of phenytoin and carbamazepine in the newborn; in Morselli, Garattini and Sereni (Eds) Basic and Therapeutic Aspects of Perinatal Pharmacology, p.341–345 (Raven Press, New York 1975).

    Google Scholar 

  • Hyde, J.S. and Floro, L.D.: Theophylline and chlorpheniramine in childhood asthma: Dose requirements for children 6 to 12 years (therapeutic orphans) and young adults 13 to 18 years of age receiving cromolyn sodium prophylaxis. Annals of Allergy 32: 73–79 (1974).

    PubMed  CAS  Google Scholar 

  • Iisalo, E. and Dahl, M.: Serum levels and renal excretion of digoxin during maintenance therapy in children. Acta Paediatrica Scandinavica 63: 699–704 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Jackson, R.H.; McHenry, J.I.; Moreland, F.B.; Raymer, W.J. and Etter, R.L.: Clinical evaluation of Elixophyllin with correlation of pulmonary function studies and theophylline serum levels in acute and chronic asthma patients. Diseases of Chest 45: 75–85 (1964).

    Article  CAS  Google Scholar 

  • Jalling, B.: Plasma and cerebrospinal fluid concentrations of phenobarbital in infants given single doses. Developmental Medicine and Child Neurology 16: 781–793 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Jalling, B.; Boreus, L.O.; Rane, A. and Sjöqvist, F.: Plasma concentrations of diphenylhydantoin in young infants. Pharmacologia Clinica 2: 200–202 (1970).

    Article  Google Scholar 

  • Jenne, J.W.; Wyze, E.; Rood, F.S. and MacDonald, F.M.: Pharmacokinetics of theophylline. Application to adjustment of the clinical dose of aminophylline. Clinical Pharmacology and Therapeutics 13: 349–360 (1972).

    CAS  Google Scholar 

  • Johnson, G.F.; Dechtiaruk, W.A. and Solomon, H.M.: Gas-chromatographic determination of theophylline in human serum and saliva. Clinical Chemistry 21: 144–147(1975).

    PubMed  CAS  Google Scholar 

  • Jusko, W.J.; Mosovich, L.L.; Gerbracht, L.M.; Matter, M.E. and Yaffe, S.J.: Enhanced elimination of dicloxacillin in patients with cystic fibrosis. Pediatrics. In press (1975).

  • Kauffman, R.E.; Shoeman, D.W.; Wan Han, S. and Azarnoff, D.L.: Absorption and excretion of clindamycin-2-phosphate in children after intramuscular injection. Clinical Pharmacology and Therapeutics 13: 704–709 (1972).

    PubMed  CAS  Google Scholar 

  • Koysooko, R.; Ellis, E.F. and Levy, G.: Relationship between theophylline concentration in plasma and saliva of man. Clinical Pharmacology and Therapeutics 15: 454–460 (1974).

    PubMed  CAS  Google Scholar 

  • Krasula, R.W.; Pellegrino, P.A.; Hastreiter, A.R. and Soyka, L.F.: Serum levels of digoxin in infants and children. Journal of Pediatrics 81: 566–569 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Krauer, B.: The development of diurnal variation in drug kinetics in the human infants; in Morselli, Garattini and Sereni (Eds) Basic and Therapeutic Aspects of Perinatal Pharmacology, p.347–356 (Raven Press, New York 1975).

    Google Scholar 

  • Kutt, H. and McDowell, F.: Management of epilepsy with diphenylhydantoin. Journal of American Medical Association 203: 969–972 (1968).

    Article  CAS  Google Scholar 

  • Levy, G.: Pharmacokinetic control of theophylline therapy; in Levy (Ed) Clinical Pharmacokinetics, p.103–110 (American Pharmaceutical Association, Washington 1974).

    Google Scholar 

  • Levy, G.; Ellis, E.F. and Koysooko, R.: Indirect plasma-theophylline monitoring in asthmatic children by determination of theophylline concentration in saliva. Pediatrics 53: 873–876 (1974).

    PubMed  CAS  Google Scholar 

  • Levy, G. and Koysooko, R.: Pharmacokinetic analysis of the effect of theophylline on pulmonary function in asthmatic children. Journal of Pediatrics 86: 789–793 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Levy, R.H.; Pitlick, W.H.; Troupin, A.S.; Green, J.R. and Neal, J.M.: Pharmacokinetics of carbamazepine in normal man. Clinical Pharmacology and Therapeutics 17:657–668(1975).

    PubMed  CAS  Google Scholar 

  • Lous, P.: Blood serum and cerebrospinal fluid levels and renal clearance of phenemal in treated epileptics. Acta Pharmacologica et Toxicologica 10: 261–280 (1954).

    Article  PubMed  CAS  Google Scholar 

  • Lund, L.: Anticonvulsant effect of diphenylhydantoin relative to plasma levels. A prospective three-year study in ambulant patients with generalized epileptic seizures. Archives of Neurology 31: 289–294 (1974).

    CAS  Google Scholar 

  • Maselli, R.; Casal, G.L. and Ellis, E.F.: Pharmacologic effects of intravenously administered aminophylline in asthmatic children. Journal of Pediatrics 76: 777–782 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Meinardi, H.: Other antiepileptic drugs. Carbamazepine; in Woodbury, Penry and Schmidt (Eds) Antiepileptic Drugs, p.487–496 (Raven Press, New York, 1972).

    Google Scholar 

  • Mitenko, P.A. and Ogilvie, R.I.: Rational intravenous doses of theophylline. New England Journal of Medicine 289: 600–603 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Møller, I. and Rist Nielsen, H.: Serum Tegretol determinations in the treatment of epileptic disorders in childhood. Acta Paediatrica Scandinavica 61: 507–510(1972).

    Article  Google Scholar 

  • Morselli, P.L.: Carbamazepine: Absorption, distribution and excretion; in Penry (Ed), Complex Partial Seizures, Advances in Neurology II. In press (Raven Press, New York 1975).

    Google Scholar 

  • Morselli, P.L.; Assael, B.M.; Gomeni, R.; Mandelli, M.; Marini, A.; Reali, E.; Visconti, U. and Sereni, F.: Digoxin pharmacokinetics during human development; in Morselli, Garattini and Sereni (Eds) Basic and Therapeutic Aspects of Perinatal Pharmacology, p.377–392 (Raven Press, New York 1975).

    Google Scholar 

  • Neill, C.A.: The use of digitalis in infants and children. Progress in Cardiovascular Diseases 7: 399–416 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Nelson, W.E.; Vaughan, V.C. and McKay, R.J.: Textbook of Pediatrics (Saunders, Philadelphia 1975).

    Google Scholar 

  • Nicholson, D.P. and Chick, T.W.: A re-evaluation of parenteral aminophylline. American Review of Respiratory Diseases 108: 241–247 (1973).

    CAS  Google Scholar 

  • Norell, E.; Lilienberg, G. and Gamstorp, I.: Systematic determination of the serum phenytoin level as an aid in the management of children with epilepsy. European Neurology 13: 232–244 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Novak, E.; Wagner, J.G. and Lamb, D.J.: Local and systemic tolerance, absorption and excretion of clindamycin hydrochloride after intramuscular administration. Internationale Zeitung Klinische Pharmakologie, Therapie & Toxikologie 3: 201–208 (1970).

    CAS  Google Scholar 

  • Penry, J.K.; Porter, R.J. and Dreifuss, F.E: Ethosuximide. Relation of plasma levels to clinical control; in Woodbury, Penry and Schmidt (Eds) Antiepileptic Drugs, p.431–441 (Raven Press, New York 1972).

    Google Scholar 

  • Pruitt, A.W.; Dayton, P.G. and Patterson, J.H.: Disposition of diazoxide in children. Clinical Pharmacology and Therapeutics 14: 73–82 (1973).

    PubMed  CAS  Google Scholar 

  • Pruitt, A.W. and Foroy, B.A.: Personal communication (1975).

  • Rane, A.: Urinary excretion of diphenylhydantoin metabolites in newborn infants. Journal of Pediatrics 85: 543–545(1974).

    Article  PubMed  CAS  Google Scholar 

  • Rane, A.; Garle, M., Borgå, O. and Sjöqvist, F.: Plasma disappearance of tiansplacentally transferred, phenytoin in the newborn studied with mass fragmentography. Clinical Pharmacology and Therapeutics 15: 39–45 (1974).

    PubMed  CAS  Google Scholar 

  • Rane, A; Höjer, B. and Wilson, J.T.: Kinetics of carbamazepine and its 10,11-epoxide metabolite in children. Clinical Pharmacology and Therapeutics. In press (1976).

  • Rane, A.; Lunde, P.K.M.; Jailing, B.; Yaffe, S.J. and Sjöqvist, F.: Plasma protein binding of diphenylhydantoin in normal and hyperbilirubinemic infants. Journal of Pediatrics 78: 877–882 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Rane, A. and Wilson, J.T.: Plasma level monitoring of diphenylhydantoin and carbamazepine in the pediatric patient. International Symposium on Clinical Pharmacy and Clinical Pharmacology (Excerpta Medica, Amsterdam 1975).

    Google Scholar 

  • Remmer, R.; Hirschmann, J. and Greiner, L.: Die Bedeutung von Kumulation und Elimination für die Dosierung von Phenytoin (Diphenylhydantoin). Deutsche Medizinische Wochenschrift 94: 1265–1272 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Rodda, B.E.; Scholz, N.E.; Gruber, C.M. and Wolen, R.L.: Evaluation of plasma concentrations of propoxyphene utilizing a hybrid principal component-analysis of variance technic. Case 1 — Equimolar dose. Toxicology and Applied Pharmacology 19: 554–562 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Sell, S. and Wilson, J.T.: Clinical Pharmacology and antibacterial spectrum of erythromycin; in Kagon (Ed) Antimicrobial Therapy, p.71–82 (Saunders, Philadelphia 1974).

    Google Scholar 

  • Sellers, E.M. and Koch-Weser, J.: Protein binding and vascular activity of diazoxide. New England Journal of Medicine 281: 1141–1145 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Sereni, F.; Perletti, L.; Marubini, E. and Mars, G.: Pharmacokinetic studies with a long acting sulfonamide in subjects of different ages. Pediatric Research 2: 29–37 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Sereni, F.; Perletti, L.; Monfredi, N. and Marini, A.: Tissue distribution and urinary excretion of a tetracycline derivative in newborn and older infants. Journal of Pediatrics 67: 299–305 (1965).

    Article  Google Scholar 

  • Shand, D.G.; Nuckolls, E.M. and Oates, J.A.: Plasma propranolol levels in adults. Clinical Pharmacology and Therapeutics 11:112–120 (1970).

    PubMed  CAS  Google Scholar 

  • Sherwin, A.L. and Robb, J.P.: Ethosuximide: Relation of plasma levels to Clinical Control; in Woodbury, Penry and Schmidt (Eds) Antiepileptic Drugs, p.443–448 (Raven Press, New York 1972).

    Google Scholar 

  • Shirkey, H.C.: Pediatric Dosage Handbook (American Pharmaceutical Association, Washington 1973).

    Google Scholar 

  • Simons, F.E.R.; Pierson, W.E. and Bierman, C.W.: Current status of the use of theophyllines in children. Pediatrics 55: 735–737(1975).

    PubMed  CAS  Google Scholar 

  • Sjöqvist, F.; Bergfors, P.G.; Borgå, O.; Lind, M. and Ygge, H.: Plasma disappearance of nortriptyline in a newborn following placental transfer from an intoxicated mother — evidence for drug metabolism. Journal of Pediatrics 80: 496–500 (1972).

    Article  PubMed  Google Scholar 

  • Soyka, L.: Clinical pharmacology of digoxin. Pediatric Clinics of North America 19: 241–256 (1972).

    PubMed  CAS  Google Scholar 

  • Svensmark, O. and Buchthal, F.: Diphenylhydantoin and phenobarbital. Serum levels in children. American Journal of Diseases of Children 108: 82–87 (1964).

    CAS  Google Scholar 

  • Symochowicz, S.; Winston, L.; Black, J.; Calensnick, B. and Tabachnick, I.I.A.: Diazoxide blood levels in man. Journal of Pharmaceutical Science 56: 912–914 (1967).

    Article  Google Scholar 

  • Uauy, R.; Shapiro, D.L.; Smith, B. and Warshaw, J.B.: Treatment of severe apnea in prematures with orally administered theophylline. Pediatrics 55: 595–598 (1975).

    PubMed  CAS  Google Scholar 

  • Van der Kleijn, E.; Collste, P.; Norlander, B.; Agurell, S. and Sjöqvist, F.: Gas chromatographic determination of ethosuximide and phensuximide in plasma and urine of man. Journal of Pharmacy and Pharmacology 25: 324–327 (1973).

    Article  PubMed  Google Scholar 

  • Verebely, K. and Inturrisi, C.E.: Disposition of propoxyphene and norpropoxyphene in man after a single oral dose. Clinical Pharmacology and Therapeutics 15: 302–309(1974).

    PubMed  CAS  Google Scholar 

  • Wagner, J.G.; Northam, J.T.; Alway, C.D. and Carpenter, O.S.: Blood levels of drug at the equilibrium state after multiple dosing. Nature 207: 1301–1302 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Waxler, S.H. and Shack, J.A.: Administration of amino-phylline (theophylline ethylenediamine). Journal of the American Medical Association 143: 736 (1950).

    Article  PubMed  CAS  Google Scholar 

  • Weinberger, M.M.; Bronsky, E.A.: Evaluation of oral bronchodilator therapy in asthmatic children. Journal of Pediatrics 84: 421–427 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Welling, P.G.; Lyons, L.L.; Craig, W.A. and Trochta, G.A.: Influence of diet and fluid of bioavailability of theophylline. Clinical Pharmacology and Therapeutics 17: 475–480(1975).

    PubMed  CAS  Google Scholar 

  • West, J.R.; Smith, H.W. and Chasis, H.: Glomerular filtration rate, effective renal blood flow, and maximal tubular excretory capacity in infancy. Journal of Pediatrics 32: 10–18(1948).

    Article  PubMed  CAS  Google Scholar 

  • Wettrell, G.; Andersson, K.E.; Bertler, Å and Lundström, N.R.: Concentrations of digoxin in plasma and urine in neonates, infants, and children with heart disease. Acta Paediatrica Scandinavica 63: 705–710 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Wilson, J.T.: Compliance with instructions in the evaluation of therapeutic efficacy: A common but frequently unrecognized major variable. Clinical Pediatrics 12: 333–340 (1973).

    PubMed  CAS  Google Scholar 

  • Wilson, J.T.: Development pharmacology. A review of its application to clinical and basic science. Annual Review of Pharmacology 12: 423–450 (1972).

    CAS  Google Scholar 

  • Wilson, J.T.: Drug compliance problems for hospitalized children; in McMahon (Ed) Principles and Techniques of Human Research and Therapeutics. In press (Futura, New York 1976).

    Google Scholar 

  • Wilson, J.T.: Pragmatic assessment of medicines available for young children and pregnant or breast-feeding women; in Morselli, Garattini and Sereni (Eds) Basic and Therapeutic Aspects of Perinatal Pharmacology p.411–421 (Raven Press, New York 1975a).

    Google Scholar 

  • Wilson, J.T.: Special problems for drugs used in children. Southern Medical Journal. In press (1975b).

  • Wilson, J.T.; Atwood, G.F. and Shand, D.G.: Disposition of propoxyphene and propranolol in children. Clinical Pharmacology and Therapeutics. In press (1975a).

  • Wilson, J.T. and Fouts, J.R.: The effect of actinomycin-D on the post-phenobarbital increases in hepatic microsomal drug metabolizing enzymes in the rat. Journal of Biological Chemistry 241: 4810–4812 (1966).

    PubMed  CAS  Google Scholar 

  • Wilson, J.T.; Höjer, B. and Rane, A.: Loading and conventional dose therapy with diphenylhydantoin in children. Kinetic profile of parent drug and main metabolite in plasma. Submitted to Clinical Pharmacology and Therapeutics (1975b).

  • Wilson, J.T. and Wilkinson, G.R.: Delivery of anticonvulsant drug therapy in epileptic patients assessed by plasma level analyses. Neurology 24: 614–623 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Wilson, J.T. and Wilkinson, G.R.: Pharmacokinetic considerations of the diphenylhydantoin (DPH)-pheno-barbital (PB) interaction in a child intoxicated with primidone. Clinical Research 21: 109 (1973).

    Google Scholar 

  • Wolen, R.L., Gruber, C.M. Jr.; Kiplinger, G.F. and Scholz, N.E.: Concentration of propoxyphene in human plasma following oral, intramuscular, and intravenous administration. Toxicology and Applied Pharmacology 19:480–492(1971).

    Article  PubMed  CAS  Google Scholar 

  • Yaffe, S.J.; Levy, G. and Matzusawa, T.: Enhancement of glucuronide conjugating capacity in a hyperbilirubinemic infant due to apparent enzyme induction by phenobarbital. New England Journal of Medicine 275: 1461–1466(1966).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology at the Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden

    Anders Rane &  John T. Wilson

  2. Division of Pediatric Clinical Pharmacology, Departments of Pediatrics and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232, USA

    Anders Rane &  John T. Wilson

Authors
  1. Anders Rane
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John T. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rane, A., Wilson, J.T. Clinical Pharmacokinetics in Infants and Children. Clin Pharmacokinet 1, 2–24 (1976). https://doi.org/10.2165/00003088-197601010-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-197601010-00002

Keywords

Search

Navigation