Skip to main content
SpringerLink
Log in

Determination of theophylline clearance in South African children

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

Theophylline clearance values in South African children were determined using 400 serum theophylline concentration measurements gathered from 109 compliant outpatients during their normal routine care. Population pharmacokinetic analysis was done using the Non-Linear Mixed Effects Model (Nonmem) to analyse the data. Nonmem was also used to estimate the influence of fixed effects (weight, age, race, gender etc) on clearance and its interindividual variability.

Gender, age, and weight raised to an iterated exponent were found to be the most important demographic fixed effect parameters influencing clearance. Race was not found to be important. The weight-adjusted values of theophylline clearance decreased with increasing age. The actual values expressed in l·h−1·kg−1 were 0.0949 for children aged 1–5 y; 0.0813 for children aged 5–9 y, and 0.0660 for children of 9–16 y. The values are similar to those reported in other studies.

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

  • Al-Banna MK, Kelman AW, Whiting B (1989) Experimental design for optimal estimation of population pharmacokinetic parameters. Europ J Clin Pharmacol 36: A229

  • Aranda JV, Grondin D, Sasynick BI (1981) Pharmacologic considerations in the therapy of neonatal apnea. Pediatr Clin North Am 28: 113–133

    Google Scholar 

  • Arnold JD, Hill GN, Sansom LN (1981) A comparison of the pharmacokinetics of theophylline in asthmatic children in the acute episode and in remission. Eur J Clin Pharmacol 20: 443–447

    Google Scholar 

  • Beal SL (1984) Population pharmacokinetic data parameter estimation based on their first two statistical moments. Drug Metab Rev 15: 173–193

    Google Scholar 

  • Beal SL, Sheiner LB (1980) The NONMEM System. Am Statistician 34: 118–119

    Google Scholar 

  • Beal SL, Sheiner LB (1982) Estimating population kinetics. CRC Crit Rev Biomed Eng 8: 195–222

    Google Scholar 

  • Beal SL, Sheiner LB (1989) NONMEM Users Guide, Part I: Users Basic Guide. Technical Report. Division of Clinical Pharmacology, University of California, San Francisco

    Google Scholar 

  • Beal S, Boeckmann AJ, Sheiner LB (1990) NONMEM Users Guide. Part VI: PREDPP Guide. Technical Report. Division of Clinical Pharmacology, University of California, San Franscisco

    Google Scholar 

  • Boeckman AJ, Beal SL, Sheiner LB (1989) NONMEM Users Guide, Part V, NM-TRAN Guide. Technical Report. Division of Clinical Pharmacology. University of California, San Francisco

    Google Scholar 

  • Brandstetter Y, Kaplanski J, Leibson V, Ben-Zvi Z (1986) The effects of estrus cycle on drug metabolism in the rat. Eur J Drug Metab Pharmacokinet 11: 251–254

    Google Scholar 

  • Dahlqvist R, Bertilisson L, Birkett DJ, Eichelbaum M, Saew J, Sjoqvist F (1984) Theophylline metabolism in relation to antiyprine, debrisoquine and sparteine metabolism. Clin Pharmacol Ther 35: 170–182

    Google Scholar 

  • Driscoll MS, Ludden TM, Casto DT, Littlefield LC (1989) Evaluation of theophylline pharmacokinetics in a paediatric population using Mixed Effects Models. J Pharmakokinet Biopharm 17: 359–389

    Google Scholar 

  • Ellis EF, Koysooko R, Levi G (1976) Pharmacokinetics of theophylline in children with asthma. Pediatrics 58: 542–547

    Google Scholar 

  • Gardner MJ, Jusko WJ (1982) Effects of age and sex on theophylline clearance in premature infants with apnea. J Pediatr 89: 829–832

    Google Scholar 

  • Gibaldi M, Perrier D (1975) Pharmacokinetics. Marcel Dekker Inc, New York

    Google Scholar 

  • Ginchansky E, Weinberger M (1977) Relationship of theophylline clearance to oral dosage in children with chronic asthma. J Pediatr 91: 655–660

    Google Scholar 

  • Grevel J, Whiting B, Kelman AW, Taylor WB, Bateman DN (1988) Population analysis of the pharmacokinetic variability of high-dose metoclopramide in cancer patients. Clin Pharmacol Ther 14: 52–63

    Google Scholar 

  • Haltom JR, Szefler SJ (1985) Theophylline absorption in young asthmatic children receiving sustained release formulations. J Pediatr 107: 805–810

    Google Scholar 

  • Hendeles L, Weinberger M (1983) Theophylline A “State of the Art” Review. Pharmacotherapy 3: 2–44

    Google Scholar 

  • Hendeles L, Vaughan M, Weinberger M, Smith G (1981) Influence of gender on theophylline dosage requirements in children with chronic asthma. Drug Intel Clin Pharmacy 15: 338–340

    Google Scholar 

  • Inaba T, Lucassen M, Kalow W (1980) Antipyrine Metabolism in the rat by three hepatic mono-oxygenases. Life Sci 26: 1977–1983

    Google Scholar 

  • Isles a, Spino M, Tabachnik et al. (1981) Theophylline disposition in cystic fibrosis. Am Rev Respir Dis 127: 417–421

    Google Scholar 

  • Joad JP, Ahrens MD, Lindgren SD et al. (1986) Extrapulmonary effects of maintenance therapy with theophylline and inhaled albuterol in patients with chronic asthma. J Allergy Clin Immunol 78: 1147–1153

    Google Scholar 

  • Jusko WJ, Gardner MJ, Mangione A, Schentag JJ, Koup JR, Vance JW (1979) Factors affecting theophylline clearance: Age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, benzodiazepines, barbiturates, and ethanol. J Pharm Sci 68: 1358–1366

    Google Scholar 

  • Kellerman G, Luyten-Kellerman, Horning M, Stafford M (1976) Elimination of antipyrine and benzo(a)pyrene metabolism in cultured human lymphocytes. Clin Pharmacol Ther 20: 72–80

    Google Scholar 

  • Lenter C (1984) Geigy Scientific Tables. Volume 3. 8th ed. Switzerland: Ciba-Geigy Ltd

    Google Scholar 

  • Leung P, Kalisker A, Bell TD (1977) Variation in theophylline clearance in young subjects. J Allergy Clin Immunol 59: 440–444

    Google Scholar 

  • Loughnan PM, Sitar DS, Olgilvie RF et al. (1976) Pharmacokinetic analysis of the disposition of intravenous theophylline in young children. J Pediatr 88: 874–879

    Google Scholar 

  • Mc Laughlin J, Nall M, Isaaca B et al. (1983) The relationships of allergies and allergy treatment to school performance and student behaviour. Ann Allergy 51: 506–510

    Google Scholar 

  • Mungall D, Ludden TM, Marshall J (1985) Population pharmacokinetics of racemic warfarin in adult patients. J Pharmacokinet Biopharm 13: 213–227

    Google Scholar 

  • Murphy MB, Dillon A, Fitzgerald MX (1980) Theophylline and depression. Br Med J 281: 1322

    Google Scholar 

  • Nafziger AN, Bertino JS (1989) Sex-related differences in theophylline pharmacokinetics. Eur J Clin Pharmacol 37: 97–100

    Google Scholar 

  • O'Malley K, Crooks J, Duke E, Stevenson IH (1971) Effect of age and sex on human drug metabolism. Br Med J 3: 607–609

    Google Scholar 

  • Pedersen S, Moller-Petersen J (1984) Erratic absorption of a slow release theophylline sprinkle product caused by food. Pediatrics 74: 634–638

    Google Scholar 

  • Rachelefsky GS, Wo J, Addson J et al. (1986) Behaviour abnormalities and poor school performance due to oral theophylline. Pediatrics 78: 1133–1138

    Google Scholar 

  • Rapport L, Coffman H, Guare R, Fenton T, de Graw C, Twarag F (1989) Effects of theophylline on behaviour and learning in children with asthma. Am J Dis Child 143: 368–372

    Google Scholar 

  • Reister EF, Pantuck EJ, Pantuck CB, Passananti GT, Vessell ES, Conney AH (1980) Antipyrine metabolism during the menstrual cycle. Clin Pharmacol Ther 28: 384–391

    Google Scholar 

  • Sheiner LB, Rosenberg B, Melmon KL (1972) Modelling of individual pharmacokinetics for computer-aided drug dosage. Comput Biomed Res 5: 441–459

    Google Scholar 

  • Sheiner LB, Rosenberg B, Marathe VV (1977) Estimation of population characteristics of pharmacokinetic parameters from routine clinical data. Clin Pharmacokinet Biopharm 5: 445–479

    Google Scholar 

  • Springer C, Goldberg B, Ben Dou I et al. (1985) Clinical physiologic and psychologic comparison of treatment by cromolyn or theophylline in childhood asthma. J Allergy Clin Immunol 76: 64–69

    Google Scholar 

  • Teunissen MWE, Srivastave AK, Breimer DD (1982) Influence of sex and oral contraceptive steroids on antipyrine metabolite formation. Clin Pharmacol Ther 24: 1361

    Google Scholar 

  • Upton RA, Sansom L, Guentert TW et al. (1980) Evaluation of the absorption from 15 commercial theophylline products indicating deficiencies in currently applied bioavailability criteria. J Pharmacokinet Biopharm 8: 229–242

    Google Scholar 

  • Weinberger M, Ginchansky E (1977) Dose-dependent kinetics of theophylline disposition in asthmatic children. J Pediatr 91: 820–824

    Google Scholar 

  • Weinberger M, Hendeles L, Bighley L (1978) The relation of product formulation to absorption of oral theophylline. N Engl J Med 229: 852–857

    Google Scholar 

  • Weinberger M, Lindgren S, Bender B et al. (1987) Effects of theophylline on learning and behaviour: Reason for concern or concern without reason. J Pediatr 111: 471–474

    Google Scholar 

  • Whiting B, Kelman AW, Grevel J (1986) Population pharmacokinetics. Theory and clinical application. Clin Pharmacokinet 11: 387–401

    Google Scholar 

  • Wilson K (1984) Sex-related differences in drug disposition in man. Clin Pharmacokinet 9: 189–202

    Google Scholar 

  • Zaske DE, Miller KW, Strem EL, Austrian S, Johnson PB (1977) Oral aminophylline therapy. Increased dosage requirements in children. J Am Med Assoc 237: 1453–1455

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Natal, Durban, South Africa

    J. H. Botha

  2. Department of Pharmacology, University of Durban-Westville, Westville, South Africa

    I. Tyrannes & R. Miller

  3. Department of Paediatrics, University of Natal, Durban, South Africa

    A. Wesley

Authors
  1. J. H. Botha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Tyrannes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Wesley
    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

Botha, J.H., Tyrannes, I., Miller, R. et al. Determination of theophylline clearance in South African children. Eur J Clin Pharmacol 44, 369–375 (1993). https://doi.org/10.1007/BF00316475

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00316475

Key words

Search

Navigation