The clinical pharmacology of oral and inhaled salbutamol

Abstract

The clinical pharmacology of 3H-salbutamol has been investigated in 12 asthm<ltic patients. Peak plasma levels of between 212 and 489 nm. were seen at one to 3 hours after an oral dose (4 to 8 mg.) in 6 patients. The drug was well absorbed and 65 to 84 per cent of the dose was excreted in the urine. There was a correlation between plasma levels and one-second forced expiratory volume (FE V,) response. Peak plasma levels after inhalation of 3H-salbutamol (0.04 to 0.10 mg.) ranged from 2.55 to 5.69 nm. and were seen at 3 to 5 hours after inhalation; 7S to 97 per cent of the inhaled dose was excreted in the urine. The FEV, rose within 10 minutes of inhalation, and the results indicate that although the maiority of an aerosol dose is swallowed, bronchodilatation is due to local deposition of salbutamol in the lung. Salbutamol was excreted unchanged and as a maior metabolite (34 to 49 per cent of the dose) not previously seen in any animal species.

The Clinical Pharmacology of Salmefamol

“…Dollery (1973) reported that the picture after administration directly into the lung was different, confirming the hypothesis that the majority of the aerosol dose is swallowed. A similar pattern has been described following the administration of salbutamol (Evans, Paterson, Richards & Walker, 1971;Walker, Evans, Richards & Paterson, 1972).…”

“…Excluding patient W.W. whose baseline FEV1 was 100% of predicted normal (Table 1), the mean FEVy before treatment was 1.2 litres and the average percentage rise following salmefamol was 44%. In a study where 4 mg oral salbutamol was given to asthmatic patients, peak levels of free drug associated with bronchodilatation were 42-54 nM (Walker et al, 1972). The patients in that study were comparable with those in the present study, their mean baseline FEV1 before salbutamol was 1.5 litres and the average percent rise above baseline was 45%.…”

“…The average baseline before salbutamol wa*s 1.5 litres and the mean percentage rise for the group was 41%. Extrapolating from the data of Walker et al (1972) the peak levels of free salbutamol would have ranged from 53.5-67 nM. Blood levels of free terbutaline after oral administration of 5 mg to normal subjects ranged from 13.7-27.6 nM (Nilsson et al, 1972).…”

Systemic beta‐adrenoceptor responses to salbutamol given by metered‐ dose inhaler alone and with pear shaped spacer attachment: comparison of electrocardiographic, hypokalaemic and haemodynamic effects.

“…Systemic absorption of inhaled salbutamol may occur following deposition in the lungs and oropharynx, and also from the gut after swallowing. Direct systemic absorption from the buccal mucosa should avoid first-pass metabolism by sulphate conjugation (Walker et al, 1972;Morgan et al, 1986;Goldstein et al, 1987). Kung et al (1987) showed that mouth washing has no effect on systemic ,B-adrenoceptor responses to salbutamol 1 mg given by MDI.…”

An assessment of the partial agonist activity of Ro 31‐1118, flusoxolol and pindolol in man.

“…The increase in systolic blood pressure produced by salbutamol has been reported previously (Corea et al, 1984) although other authors have shown a fall (Mc Devitt et al, 1975) or no change (Walker et al, 1972;Watson & Richens, 1974). Salbutamol has been shown to improve indices of myocardial contractility (Sharma & Goodwin, 1978;Bourdillon et al, 1980) although it is not clear if this is due to a positive inotropic effects or a reduction in afterload caused by vasodilation.…”