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Clinical pharmacokinetics of terbutaline in humans: a systematic review

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Abstract

Terbutaline is used for the management of bronchospasm associated with asthma, bronchitis, emphysema, and chronic obstructive pulmonary disease. A systematic review would be beneficial to assess the impact of routes of administration, stereoisomerism, disease states, smoking, age, exercise, and chronobiology on pharmacokinetics (PK) of terbutaline in humans. PubMed and Google Scholar databases were searched to screen all the relevant articles consisting of at least one of the PK parameters after administration of oral, inhaled, and intravenous (IV) terbutaline in humans. Oral studies of terbutaline depicted a linear relationship between plasma concentration (Cp) and the administered dose. The IV studies demonstrated multi-exponential behavior for disposition and renal clearance. Higher systemic availability was observed with inhaled as compared to oral route, and chrono-pharmacokinetic behavior was notable. Time to reach maximum plasma concentration (Tmax) was prolonged, and maximum plasma concentration (Cmax) was lowered after exercise. The primary route of excretion in chronic kidney disease (CKD) patients is reported to be nonrenal. In pregnant women, the Cp of terbutaline is lowered and clearance is increased. The addition of theophylline to terbutaline did not affect the PK of terbutaline; hence, both can be used without dose adjustment. This review summarizes all the available PK parameters of terbutaline, and it may be helpful for researchers in the development and evaluation of PK models as well as in designing optimal dosage regimens in different clinical conditions.

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References

  • Ahuja S, Ashman J (1990) Terbutaline sulfate, in Analytical profiles of drug substances. 19:601–625. Academic press 

  • Al-Dirini RM, Thewlis D, Paul G (2012) A comprehensive literature review of the pelvis and the lower extremity FE human models under quasi-static conditions. Work 41(Suppl 1):4218–4229

    Article  Google Scholar 

  • Aschenbrenner DS (2011) Warning against using terbutaline to prevent preterm labor. AJN Am J Nurs 111(6):24

    Google Scholar 

  • Bastiansen A, Eggert S, Pedersen E (2013) Pharmacokinetics of terbutaline in chronic kidney disease. Eur J Clin Pharmacol 69(11):1951–1954

    Article  CAS  Google Scholar 

  • Beltagi AM, El-Desoky HS, Ghoneim MM (2007) Quantification of terbutaline in pharmaceutical formulation and human serum by adsorptive stripping voltammetry at a glassy carbon electrode. Chem Pharm Bull (tokyo) 55(7):1018–1023

    Article  CAS  Google Scholar 

  • Bengtsso B, Fagerstrom PO (1982) Extrapulmonary effects of terbutaline during prolonged administration. Clin Pharmacol Ther 31(6):726–732

    Article  Google Scholar 

  • Berg G, Lindberg C, Rydén G (1984) Terbutaline in the treatment of preterm labour. Eur J Respir Dis Suppl 134:219–230

    CAS  Google Scholar 

  • Berger VW, Alperson SY (2009) A general framework for the evaluation of clinical trial quality. Rev Recent Clin Trials 4(2):79–88

    Article  Google Scholar 

  • Billing B et al (1982) Separate and combined use of terbutaline and theophylline in asthmatics Effects related to plasma levels. Eur J Respir Dis 63(5):399–409

    CAS  Google Scholar 

  • Boréus LO, de Château PU (1982) Terbutaline in breast milk. Br J Clin Pharmacol 13(5):731–732

    Article  Google Scholar 

  • Borgstrom L et al (1989) Pharmacokinetic evaluation in man of terbutaline given as separate enantiomers and as the racemate. Br J Clin Pharmacol 27(1):49–56

    Article  CAS  Google Scholar 

  • Borgström L, Chang-Xiao L, Walhagen A (1989) Pharmacokinetics of the enantiomers of terbutaline after repeated oral dosing with racemic terbutaline. Chirality 1(2):174–177

    Article  Google Scholar 

  • Bradley SE et al (1956) The effect of exercise on the splanchnic blood flow and splanchnic blood volume in normal man. Clin Sci 15(3):457–463

    CAS  Google Scholar 

  • Cazzola M et al (2012) Pharmacology and therapeutics of bronchodilators. Pharmacol Rev 64(3):450–504

    Article  CAS  Google Scholar 

  • Chawanpaiboon S, Laopaiboon M, Lumbiganon P, Sangkomkamhang US, Dowswell T (2014) Terbutaline pump maintenance therapy after threatened preterm labour for reducing adverse neonatal outcomes. Cochrane Database Syst Rev (3)

  • Costill DL, Fink WJ (1974) Plasma volume changes following exercise and thermal dehydration. J Appl Physiol 37(4):521–525

    Article  CAS  Google Scholar 

  • Dahl R et al (1988) Terbutaline sustained-release tablets in nocturnal asthma–a placebo-controlled comparison between a high and a low evening dose. Br J Dis Chest 82(3):237–241

    Article  CAS  Google Scholar 

  • Dyreborg A et al (2016) Pharmacokinetics of oral and inhaled terbutaline after exercise in trained men. Front Pharmacol 7:150

    Article  Google Scholar 

  • Elers J et al (2012) Urine and serum concentrations of inhaled and oral terbutaline. Int J Sports Med 33(12):1026–1033

    Article  CAS  Google Scholar 

  • Fagerström PO (1984) Pharmacokinetics of terbutaline after parenteral administration. Eur J Respir Dis Suppl 134:101–110

    Google Scholar 

  • Faiyazuddin M et al (2011) A validated HPTLC method for determination of terbutaline sulfate in biological samples: application to pharmacokinetic study. Saudi Pharm J 19(3):185–191

    Article  CAS  Google Scholar 

  • Fuglsang G, Pedersen S, Borgström L (1989) Dose-response relationships of intravenously administered terbutaline in children with asthma. J Pediatr 114(2):315–320

    Article  CAS  Google Scholar 

  • Garofolo MC et al (2002) Beta-adrenergic modulation of muscarinic cholinergic receptor expression and function in developing heart. Am J Physiol Regul Integr Comp Physiol 282(5):R1356–R1363

    Article  CAS  Google Scholar 

  • Gaudet LM et al (2012) Effectiveness of terbutaline pump for the prevention of preterm birth. A systematic review and meta-analysis. PLoS One 7(2):e31679

    Article  CAS  Google Scholar 

  • Hochhaus G, Möllmann H (1992) Pharmacokinetic/pharmacodynamic characteristics of the beta-2-agonists terbutaline, salbutamol and fenoterol. Int J Clin Pharmacol Ther Toxicol 30(9):342–362

    CAS  Google Scholar 

  • Hultquist C et al (1989) Pharmacokinetics of intravenous terbutaline in asthmatic children. Dev Pharmacol Ther 13(1):11–20

    Article  CAS  Google Scholar 

  • Ingemarsson I et al (1981) Single injection of terbutaline in term labor: placental transfer and effects on maternal and fetal carbohydrate metabolism. Am J Obstet Gynecol 139(6):697–701

    Article  CAS  Google Scholar 

  • Jonkman J et al (1988) Theophylline-terbutaline, a steady state study on possible pharmacokinetic interactions with special reference to chronopharmacokinetic aspects. Br J Clin Pharmacol 26(3):285–293

    Article  CAS  Google Scholar 

  • Karabey Y, Sahin S, Oner L, Hincal AA (2003) Bioavailability file: terbutaline. Fabad j pharm Sci 28:149–160

    CAS  Google Scholar 

  • Kendall MJ et al (1982) Cardiovascular and metabolic effects of terbutaline. J Clin Hosp Pharm 7(1):31–36

    CAS  Google Scholar 

  • Khazaeinia T, Ramsey AA, Tam YK (2000) The effects of exercise on the pharmacokinetics of drugs. J Pharm Pharm Sci 3(3):292–302

    CAS  Google Scholar 

  • Koëter GH et al (1985) Effect of oral slow-release terbutaline on early morning dyspnoea. Eur J Clin Pharmacol 28(2):159–162

    Article  Google Scholar 

  • Kola R, Ramani DN, Kumar PB (2013) Formulation and in-vitro evaluation of terbutaline sulphate sustained release tablets. Indian J Res Pharm Biotechnol 1(5):621

    Google Scholar 

  • Kreiberg M et al (2017) Influence of exercise in normal and hot ambient conditions on the pharmacokinetics of inhaled terbutaline in trained men. Scand J Med Sci Sports 27(7):692–703

    Article  CAS  Google Scholar 

  • Lam F, Gill P (2005) Beta-agonist tocolytic therapy. Obstet Gynecol Clin North Am 32(3):457–484

    Article  Google Scholar 

  • Lebovitz DJ et al (2004) Pharmacokinetic properties and tolerability of single-dose terbutaline in patients with severe asthma treated in the pediatric intensive care unit. Curr Ther Res Clin Exp 65(1):98–109

    Article  CAS  Google Scholar 

  • Leferink JG, Wagemaker-Engels I, Maes RA (1977) Quantitative analysis of terbutaline in serum and urine at therapeutic levels using gas chromatography–mass spectrometry. J Chromatogr 143(3):299–305

    Article  CAS  Google Scholar 

  • Lima JJ et al (2005) Influence of sex and beta2 adrenergic receptor haplotype on resting and terbutaline-stimulated whole body lipolysis. Metabolism 54(4):492–499

    Article  CAS  Google Scholar 

  • Lorino AM et al (1989) Effects of sustained exercise on pulmonary clearance of aerosolized 99mTc-DTPA. J Appl Physiol (1985) 67(5):2055–9

    Article  CAS  Google Scholar 

  • Lyrenäs S et al (1986) Pharmacokinetics of terbutaline during pregnancy. Eur J Clin Pharmacol 29(5):619–623

    Article  Google Scholar 

  • Mizuma T et al (2005) Differentiation of organ availability by sequential and simultaneous analyses: intestinal conjugative metabolism impacts on intestinal availability in humans. J Pharm Sci 94(3):571–575

    Article  CAS  Google Scholar 

  • Morgan DJ (1990) Clinical pharmacokinetics of beta-agonists. Clin Pharmacokinet 18(4):270–294

    Article  CAS  Google Scholar 

  • Nightingale SL (1998) Warning on use of terbutaline sulfate for preterm labor. JAMA 279(1):9–9

    Article  CAS  Google Scholar 

  • Nyberg L (1984) Pharmacokinetic parameters of terbutaline in healthy man. An overview. Eur J Respir Dis Suppl 134:149–60

    CAS  Google Scholar 

  • Nyberg L et al (1998) Pharmacokinetics of bambuterol in healthy subjects. Br J Clin Pharmacol 45(5):471–478

    Article  CAS  Google Scholar 

  • Obach RS, Lombardo F, Waters NJ (2008) Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Drug Metab Dispos 36(7):1385–1405

    Article  CAS  Google Scholar 

  • Paixão P, Gouveia LF, Morais JA (2012) Prediction of the human oral bioavailability by using in vitro and in silico drug related parameters in a physiologically based absorption model. Int J Pharm 429(1–2):84–98

    Article  Google Scholar 

  • Pauwels R et al (1986) A comparison of the clinical and bronchodilating effects of plain and slow-release tablets of terbutaline at steady state. Br J Clin Pharmacol 21(2):217–222

    Article  CAS  Google Scholar 

  • Philip-Joet F et al (1992) Effects of a constant dose rate of terbutaline on circadian peak expiratory flow, heart rate and systolic arterial pressure in patients with asthma exacerbation. Respiration 59(4):197–200

    Article  CAS  Google Scholar 

  • Philipson A (1977) Pharmacokinetics of ampicillin during pregnancy. J Infect Dis 136(3):370–376

    Article  CAS  Google Scholar 

  • Sayed S et al (2013) Fast-dissolving sublingual films of terbutaline sulfate: formulation and in vitro/in vivo evaluation. Mol Pharm 10(8):2942–2947

    Article  CAS  Google Scholar 

  • Schmekel B, Borgström L, Wollmer P (1991) Difference in pulmonary absorption of inhaled terbutaline in healthy smokers and non-smokers. Thorax 46(4):225–228

    Article  CAS  Google Scholar 

  • Schmekel B, Borgström L, Wollmer P (1992) Exercise increases the rate of pulmonary absorption of inhaled terbutaline. Chest 101(3):742–745

    Article  CAS  Google Scholar 

  • Tegnér K et al (1984) Elimination pathways of terbutaline. Eur J Respir Dis Suppl 134:93–100

    Google Scholar 

  • Wettrell G et al (1986) Terbutaline slow-release tablets in children with bronchial asthma. Effect and pharmacokinetics compared with plain terbutaline tablets. Allergy 41(6):418–22

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors will like to thank the Dean, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan, for providing the infrastructure for carrying out this research.

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Authors and Affiliations

  1. Department of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, 60800, Pakistan

    Khadeeja Sultan, Ammara Zamir, Anees ur Rehman, Abdul Majeed & Muhammad Fawad Rasool

  2. Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, 60800, Pakistan

    Waseem Ashraf & Imran Imran

  3. Allama Iqbal Campus, University College of Pharmacy, University of the Punjab, Lahore, 54000, Pakistan

    Hamid Saeed

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  1. Khadeeja Sultan
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Contributions

Conceptualization: Khadeeja Sultan, Ammara Zamir, Abdul Majeed, Imran, Waseem Ashraf, Muhammad Fawad Rasool; methodology: Khadeeja Sultan, Muhammad Fawad Rasool; Waseem Ashraf, Imran, Hamid Saeed, Anees ur Rehman; formal analysis and investigation: Khadeeja Sultan, Ammara Zamir, Muhammad Fawad Rasool, Anees ur Rehman, Hamid Saeed, Abdul Majeed; writing — original draft preparation: Khadeeja Sultan, Ammara Zamir, Muhammad Fawad Rasool, Waseem Ashraf; writing — review and editing: Khadeeja Sultan, Ammara Zamir, Muhammad Fawad Rasool, Imran Imran, Hamid Saeed, Abdul Majeed, Anees ur Rehman; supervision: Muhammad Fawad Rasool. All authors read and approved the final manuscript.

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Correspondence to Muhammad Fawad Rasool.

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Sultan, K., Zamir, A., Ashraf, W. et al. Clinical pharmacokinetics of terbutaline in humans: a systematic review. Naunyn-Schmiedeberg's Arch Pharmacol 396, 213–227 (2023). https://doi.org/10.1007/s00210-022-02304-5

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