Pharmacokinetics Of Salbutamol Research Articles

Clinical pharmacology of salbutamol in infants and children

Inhaled β2 agonists are the bronchodilator treatment of choice in asthma because they are the most effective bronchodilators. β2 agonists may cause bronchodilation by inhibiting the release of bronchoconstrictor neurotransmitters from airway nerves. Inhaled short-acting β2 agonists are the most widely used and effective bronchodilators for the treatment of asthma due to their functional antagonisms of bronchoconstriction. Salbutamol is a short-acting β-adrenergic agonist widely used by asthmatics for its bronchodilator activity. Salbutamol is a racemic mixture of active R-salbutamoland inactive S-salbutamol. In infants, salbutamol is administered by nebulizer solution at a dose of 2.5 mg trice-daily to treat chronic lung disease. In children, salbutamol may be administered intravenously, by inhalational, nebulisation, or orally and salbutamol dose varies with the child's age. The efficacy and safety of salbutamol have been extensively studied in infants and children and salbutamol is sulphatedin-vivo in patients and in-vitro in human lung, liver, and duodenum and the sulfation-rate remarkably varies among patients and among lung, liver, and duodenum specimens. The pharmacokinetics of salbutamol have been studied in infants and children and the elimination half-life of salbutamol is 2.2 hours in infants and about 6 years in children. The treatment of infants and children with salbutamol has been extensively studied and salbutamol poorly crosses the human placenta. The aim of this study is to review the salbutamol dosing, efficacy and safety, pharmacokinetics, and treatment in infants and children and salbutamol metabolism and transfer across the human placenta.

Pharmacokinetics and safety of salbutamol/ambroxol fixed-dose combination granules in healthy Chinese subjects .

The aim of the study was to investigate the pharmacokinetics and tolerability of salbutamol/ambroxol fixed-dose combination granules following single and multiple dosing in healthy Chinese subjects. This was a randomized, open-label, two-period, one-sequence study (n = 12). Each subject received a single oral dose in period 1 and multiple doses in period 2. Plasma concentrations of these two components were determined using a validated LC-MS/MS method. Adverse events (AEs) were documented throughout the study. Investigators evaluated AEs in terms of frequency, duration, intensity, seriousness, outcome, and relationship to study drugs. Following single dosing, Cmax values were 8.07±1.31 ng/mL and 25.7±6.5 ng/mL for salbutamol and ambroxol, respectively. The corresponding T1/2 values were 8.15±3.13 hours and 9.31±2.27 hours, respectively. Moreover, no statistical differences in the pharmacokinetics of salbutamol and ambroxol in subjects receiving single or multiple dosage were observed. Single- and multiple-dose oral administration of fixed-dose combination granules were safe and well tolerated in healthy Chinese subjects. Drug hypersensitivity syndrome did not occur during our study. The pharmacokinetics of salbutamol and ambroxol in the fixed-dose combination granules were not affected by dosing duration, and gender differences seemed to have no effect on the pharmacokinetics of salbutamol and ambroxol after a single dose and multiple doses of the medication. .

Validation of a confirmatory method of salbutamol in sheep hair by UPLC-MS/MS and its application to pharmacokinetic study

A new method for determining salbutamol in hair of sheep by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was established. Samples were extracted with 0.1M of HCl solution. The mixture was heated to 60°C in a water bath and kept at this temperature for 4h. The extracts were purified through SPE method and then dried with nitrogen. Residues were redissolved in mobile phase. The target compound was determined by UPLC-MS/MS with BEH-C18 column. The usefulness and feasibility of different treatment procedures of hair containing salbutamol were evaluated. The range of linearity was 1–100ng/g. The LOD was 0.3ng/g, and the LOQ was 1ng/g. Recoveries were 89–106%, and coefficients of variation were 3.2–13.9%. Pharmacokinetics of salbutamol was studied in healthy sheep after oral administration of 150μg/kg body weight salbutamol for 21 consecutive days. Salbutamol residues in hair were still detected after 21 days of administration.

Investigation of urinary levels of salbutamol in asthmatic patients receiving inhaled therapy.

Some studies have indicated that over-reliance on inhaled bronchodilator (beta 2-agonist) therapy may worsen asthma control and increase morbidity. The aim of this study was to measure urinary concentrations of salbutamol, the most commonly used bronchodilator, in a relatively large sample of asthmatic patients and examine the potential value of the concentration as an indicator of over-use of salbutamol. The urinary concentrations of the drug were measured in 'spot' urine samples from 102 asthmatic patients (64 community patients and 38 hospital inpatients). A solid-phase extraction technique, using a phenyl-bonded phase and a reversed-phase ion-pair high-performance liquid chromatography assay with UV-detection were developed and used to measure both unchanged salbutamol concentrations and total salbutamol concentrations after enzymatic hydrolysis of the metabolite. In addition, salbutamol concentrations were corrected for urine dilution, with the measured drug expressed per gram of urinary creatinine. The hospital patients were generally older, had greater disease severity, were more likely to be receiving prophylactic therapy and had received more salbutamol in the past 24 h. The urinary concentrations of salbutamol varied enormously between patients. The median concentrations of unchanged and total drug were 0.38 microgram/ml (range 0-34.4 micrograms/ml) and 2.55 micrograms/ml (range 0-49.8 micrograms/ml), respectively. Even when controlling for dosage in the preceding 24 h, there was a 262-fold and 810-fold variation in the urinary concentrations for unchanged and total salbutamol, respectively, among the community patients. Modest correlations were found between salbutamol concentrations and dosage administered in the preceding 24 h (Spearman's r = 0.67 and 0.54 for unchanged and total drug, respectively; P < 0.001). The correlations improved only slightly with correction for urine dilution (Spearman's r = 0.69 and 0.57 for unchanged and total drug, respectively; P < 0.001). This enormous inter-patient variability, which may be largely due to differences in the pharmacokinetics of salbutamol and inhaler technique, may play a role in the observed worsening of asthma control with the regular use of inhaled bronchodilator drugs and warrants further investigation. Measuring urinary concentrations of salbutamol in spot samples provides only a relatively crude indication of the extent of use of inhaled salbutamol in the preceding 24 h.

Pharmacokinetics and metabolism of salbutamol in premature labour.

1 The pharmacokinetics of salbutamol and its sulphate conjugate were examined during intravenous and steady-state oral administration in nine patients receiving the drug for the prevention or treatment of premature labour. 2 Uterine contractions were inhibited by plasma salbutamol concentrations in the range 8-33 ng ml-1 in six of the seven patients who were receiving intravenous drug. 3 By comparison with our previous study in a control group of healthy males and nonpregnant females, the total clearance of salbutamol in premature labour (501; s.d. 185 ml min-1) was similar to that in the control group (480; s.d. 123 ml min-1). Renal salbutamol clearance (208; s.d. 51 ml min-1), however, was significantly less than that in the control group (283; s.d. 51 ml min-1). 4 The systemic availability (n = 3), urinary recovery of unchanged oral salbutamol and area under the plasma curve during the oral dosage interval (n = 5) were all only slightly lower (10-20%) than control values, suggesting slightly lower oral absorption. 5 Formation and elimination of the sulphate conjugate were similar to those observed in control subjects suggesting that first-pass sulphation in the gut wall is unchanged in pregnancy. Overall there were only minor differences in salbutamol pharmacokinetics between control subjects and patients in premature labour.

Pharmacokinetics of intravenous and oral salbutamol and its sulphate conjugate.

The pharmacokinetics of salbutamol and its sulphate conjugate metabolite were investigated after intravenous and steady-state oral administration of salbutamol to 10 healthy volunteers. With intravenous administration, total plasma clearance was 480 +/- 123 ml min-1, elimination half-life was 3.86 +/- 0.83 h and apparent volume of distribution was 156 +/- 381. Urinary excretion of unchanged drug and sulphate conjugate were 64.2 +/- 7.1% and 12.0 +/- 3.1% of the dose, respectively. With oral administration, systemic availability was 0.50 +/- 0.04, and urinary excretion of unchanged drug and sulphate conjugate were 31.8 +/- 1.9% and 48.2 +/- 7.3% of the dose, respectively. The drug eliminated on the first-pass could be accounted for entirely as sulphate conjugate formed, presumably, in the intestinal wall. Renal clearance of salbutamol was 291 +/- 70 ml min-1 after intravenous and 272 +/- 38 ml min-1 after oral administration, while the renal clearance of the sulphate conjugate was 98.5 +/- 23.5 ml min-1 after oral administration. Heart rate increased with increasing plasma salbutamol concentration, although a lag was evident. The effect on heart rate was lower after 24 h continuous oral salbutamol administration.