Metabolic studies of salbutamol-3H: A new bronchodilator, in rat, rabbit, dog and man

Martin, Lee; Hobson, Joshua C.; Page, Jean A.; Harrison, C.

doi:10.1016/0014-2999(71)90211-1

Cited by 90 publications

(23 citation statements)

References 9 publications

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“…In healthy males and nonpregnant females, absorption of orally administered salbutamol is virtually complete (Martin et al, 1971;Walker et al, 1972;Evans et al, 1973). In the present study, the systemic availability, urinary recovery of unchanged salbutamol and AUC during the dosage interval were all lower than values recorded in the control group (Table 3).…”

Section: Nscontrasting

confidence: 57%

“…In healthy males and nonpregnant females the major route of elimination of intravenously administered salbutamol is renal excretion, whereas that of orally administered drug is conjugation with sulphate in the gut wall (Martin et al, 1971;Walker et al, 1972;Evans et al, 1973; Table 3 Pharmacokinetics of intravenous and oral salbutamol in premature labour and in a control group* of healthy males and nonpregnant females…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics and metabolism of salbutamol in premature labour.

Hutchings

Paull

Wilson‐Evered

et al. 1987

Brit J Clinical Pharma

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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.

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Section: Nscontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and metabolism of salbutamol in premature labour.

Hutchings

Paull

Wilson‐Evered

et al. 1987

Brit J Clinical Pharma

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“…It is to be noted that previous studies had also demonstrated the sulfation of salbutamol in the human lung, liver and intestine (48 50). It is noteworthy that although glucuronidation of salbutamol has not been reported in humans, glucuronide metabolites have been detected in other species including bovine, rabbit and rat (14,45,51). Although the metabolism and conjugation reactions of ractopamine in humans have not been investigated, both sulfate and glucuronide metabolites of ractopamine have been detected in livestock including turkey and swine (13).…”

Section: Discussionmentioning

confidence: 99%

Sulfation of ractopamine and salbutamol by the human cytosolic sulfotransferases

Kurogi

Davidson

et al. 2012

Journal of Biochemistry

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-Cheh Liu *These two authors contributed equally to this study.Feed additives such as ractopamine and salbutamol are pharmacologically active compounds, acting primarily as b-adrenergic agonists. This study was designed to investigate whether the sulfation of ractopamine and salbutamol may occur under the metabolic conditions and to identify the human cytosolic sulfotransferases (SULTs) that are capable of sulfating two major feed additive compounds, ractopamine and salbutamol. A metabolic labelling study showed the generation and release of [ 35 S]sulfated ractopamine and salbutamol by HepG2 human hepatoma cells labelled with [ 35 S]sulfate in the presence of these two compounds. A systematic analysis using 11 purified human SULTs revealed SULT1A3 as the major SULT responsible for the sulfation of ractopamine and salbutamol. The pH dependence and kinetic parameters were analyzed. Moreover, the inhibitory effects of ractopamine and salbutamol on SULT1A3-mediated dopamine sulfation were investigated. Cytosol or S9 fractions of human lung, liver, kidney and small intestine were examined to verify the presence of ractopamine-/ salbutamol-sulfating activity in vivo. Of the four human organs, the small intestine displayed the highest activity towards both compounds. Collectively, these results imply that the sulfation mediated by SULT1A3 may play an important role in the metabolism and detoxification of ractopamine and salbutamol.

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“…Although the relative effects on uterine muscle are unknown, comparison of equimolar doses should give some ideal of the ratio of therapeutic to side effects, In this study there were no differences in the molar dose response relationships where they could be compared (insulin, potassium, phosphate, heart rate) and generally rimiterol and salbutamol have a similar spectrum of adrenoreceptor activity. If therapeutic, metabolic and cardiovascular effects are similar, rimiterol has the practical advantage of having a much shorter plasma half life-l-3 min (Griffin, Williams & Maughan 1973) v 30-120 min (Evans, Walker, Brittain & Paterson, 1973;Martin, Hobson, Page & Harrison, 1971). This means a steady state is reached more quickly when the infusion is started and side effects regress more quickly when the infusion is stopped.…”

Section: Methodsmentioning

confidence: 99%

Metabolic and cardiovascular side effects of the beta 2‐adrenoceptor agonists salbutamol and rimiterol.

Phillips¹,

Vedig²,

Jones³

et al. 1980

Brit J Clinical Pharma

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The metabolic and cardiovascular side‐effects of intravenous infusions of therapeutic doses of beta 2‐adrenoceptor agonists salbutamol and rimiterol have been determined in four healthy male subjects. There were dose‐related increases in plasma glucose, renin activity, serum insulin and heart rate, and significant hyperlactataemia and ketonaemia. There were dose‐related decreases in plasma potassium, phosphate and corticosteroids and significant hypocalcaemia and hypomagnesaemia. The effects of equivalent molar amounts of salbutamol and rimiterol were similar. Whichever drug is used, special care is required with patients who may have abnormal glucose tolerance, potassium depletion, or be predisposed to lactic acidosis. Rimiterol may be preferable for infusion because of its short plasma half‐life.

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Metabolic studies of salbutamol-3H: A new bronchodilator, in rat, rabbit, dog and man

Cited by 90 publications

References 9 publications

Pharmacokinetics and metabolism of salbutamol in premature labour.

Pharmacokinetics and metabolism of salbutamol in premature labour.

Sulfation of ractopamine and salbutamol by the human cytosolic sulfotransferases

Metabolic and cardiovascular side effects of the beta 2‐adrenoceptor agonists salbutamol and rimiterol.

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