Summary
Fifteen patients with asthma were given salbutamol controlled-release (SCR) 4 mg or 8 mg twice daily for seven days, in a randomised double-blind cross-over design. Plasma salbutamol levels were measured after the first and fifteenth doses for a 12 h period following drug ingestion.
At steady-state the geometric mean values for Cmax were 8.2 ng/ml for 4 mg, and 16.1 ng/ml for 8 mg. Median tmax values were 300 and 240 min respectively. The geometric mean AUC (0–12) were 4507 ng·min·ml−1 and 8980 ng·min/ml. Peak to trough fluctuation ratios were 0.577 and 0.572.
There were no significant differences between 4 mg or 8 mg formulations, for any of the parameters measured, after appropriate corrections for dose. The concentration-time profiles at steady-state showed little fluctuation in plasma salbutamol levels over the twelve hour dosing interval. These results show that 4 mg and 8 mg formulations of SCR provide smooth plasma profiles at steady-state with a twice daily dosing regime.
Similar content being viewed by others
References
Britton M (1988) A multicentre comparison of 8 mg salbutamol controlled release (SCR) tablets b. d. versus theophylline slow release tablets (300 mg) b. d. in control of reversible airways obstruction. Eur Respir J [Suppl 2] 1: 197s
Callaghan B, Ryan W, Hagstad H, Tegner K, Kotaniemi J (1986) A multicentre study of a new controlled-release formulation of salbutamol (salbutamol CR) compared with a titrated dose of slow-release theophylline (Theodur) in the treatment of chronic obstructive airways disease. Bull Eur Physiopathol Respir [Suppl 8] 22: 1115
Cochran WG, Cox GM (1957) Note on the statistical analysis of the results: In: Experimental designs. Wiley, New York, pp 45–94
Crompton GK (1982) Problems patients have using pressurised aerosol inhalers. Eur J Respir Dis [Suppl 119] 63: 101–104
Dahl R (1988) A multicentre trial of salbutamol controlled release tablets (volmax) and standard salbutamol tablets (ventolin) in the management of asthma and chronic bronchitis. Eur Respir J [Suppl 2] 1: 306s
Davies RJ, Ferguson H, Herdman MJ, Ollier S (1988) Oral controlled release albuterol: its effect on asthmatic symptoms and bronchial hyperresponsiveness. Am Rev Respir Dis [Suppl] 137: 32
Hutchings MJ, Paull JD, Morgan DJ (1983) Determination of salbutamol in plasma by high performance liquid chromatography with fluorescence detection. J Chromatogr 277: 423–426
Jenne JG, Chick TW, Strickland RD, Wall FJ (1977) Subsensitivity of beta-responses during therapy with a long acting beta-2 preparation. J Allergy Clin Immunol 59: 383–390
Jenne JW, Valcarenghi G, Druz WS, Starkey PW, Yu C, Shaughnessy TK (1986) Comparison of tremor responses to orally administered albuterol and terbutaline. Am Rev Respir Dis 134: 708–713
Koch GG (1972) The use of nonparametric methods in the Statistical analysis of the two-period change-over design. Biometrics 28: 577–588
Legge JS, Gaddie J, Palmer KNV (1971) Comparison of two oral selective beta-2 adrenergic stimulant drugs in bronchial asthma. Br Med J I: 637–639
Maesen FP, Measen V, Smeets JJ (1986) Comparison of a controlled release tablet of salbutamol given twice daily with a standard tablet given four times daily in the management of chronic obstructive lung disease. Eur J Clin Pharmacol 31: 431–436
Milroy R, Carter R, Carlyle DL, Boyd G (1987) Pharmacology of salbutamol with a new controlled release salbutamol preparation. Am Rev Respir Dis [Suppl] 135: A228
Morgan DJ, Paull JD, Richmond BH, Wilson-Evered E, Ziccone SP (1986) Pharmacokinetics of intravenous and oral salbutamol and its sulphate congugate. Br J Clin Pharmacol 22: 587–593
Neilson NH, Weeke B, Ostlener L, Wilkinson P, Kay A, Williams I, Ng SH, Wouters FM, Beamer HM (1988) Salbutamol controlled release (Volmax) — A comparison with standard salbutamol tablet (ST) in the treatment of chronic obstructive airway disease (COAD). Eur Respir J [Suppl 2] 1: 306s
Nelson HS, Raine D Jr, Doner C, Posey WC (1977) Subsensetivity to the bronchodilator action of albuterol produced by chronic administration. Am Rev Respir Dis 116: 871–878
Sykes RS, Reese ME, Meyer MC (1987) Pharmacokinetic properties of a new sustained-release albuterol preparation, volmax. J Allergy Clin Immunol 79: 152
Theeuwes F (1975) Elementary osmotic pump. J Pharm Sci 64: 1987–1991
Tsanakas JN, Bannister OH, Baxter P (1988) Tachyphylaxis does not occur after long-term administration of salbutamol controlled release (Volmax: SCR). Eur Respir J [Suppl 2] 1: 202s
Walker SR, Evans ME, Richards AJ, Paterson JW (1972) The clinical pharmacology of oral and inhaled salbutamol. Clin Pharmacol Ther 13: 861–867
Watson JM, Richens A (1974) The effects of salbutamol and terbutaline on physiological tremor, bronchial tone and heart rate. Br J Clin Pharmacol 1: 223–227
Author information
Authors and Affiliations
Additional information
Part of this paper has been presented in abstract form to the British Thoracic Society, Newcastle, July 1988
Rights and permissions
About this article
Cite this article
Lipworth, B.J., Clark, R.A., Dhillon, D.P. et al. Single dose and steady-state pharmacokinetics of 4 mg and 8 mg oral salbutamol controlled-release in patients with bronchial asthma. Eur J Clin Pharmacol 37, 49–52 (1989). https://doi.org/10.1007/BF00609424
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00609424