Deuterium Isotope Effects on Degradation of Hydrocortisone in Aqueous Solution

Pitman, Ian H.; Higuchi, Takeru; Alton, M.; Wiley, Robert A.

doi:10.1002/jps.2600610619

Cited by 13 publications

(4 citation statements)

References 6 publications

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“…Pitman et al (90) synthesized hydrocortisone (I) in which two deuterium atoms were incorporated in the C-21 position. Its stability against degradation in aqueous solution under both aerobic and anaerobic conditions was compared with that of hydrocorti-…”

mentioning

confidence: 99%

Studies with Deuterated Drugs

Blake

Crespi

Katz

1975

Journal of Pharmaceutical Sciences

116

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mentioning

confidence: 99%

Studies with Deuterated Drugs

Blake

Crespi

Katz

1975

Journal of Pharmaceutical Sciences

116

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“…Hydrocortisone exhibits very slow degradation in aqueous solution at pH 8.4 (Takubo et al, 1962;Pitman et al, 1972;Cornejo et al, 1980). However, degradation occurs more rapidly in contact with sepiolite (Hermosin et al, 1981) and even more rapidly in contact with palygorskite (Cornejo et al, 1980) and seems to consist of two, apparent first-order reactions rather than the simple apparent first-order reaction observed for hydrocortisone solutions.…”

Section: Mechanism Of Hydrocortisone Reaction On the Claymentioning

confidence: 99%

Role of Ferric Iron in the Oxidation of Hydrocortisone by Sepiolite and Palygorskite

Cornejo

Hermosı́n

White

et al. 1983

Clays and clay miner.

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Abstract--The role of adsorbed and structural Fe n+ in palygorskite and sepiolite with respect to the oxidation of hydrocortisone in aqueous suspension has been evaluated using electron spin resonance and UVvisible spectroscopy. Natural surface-adsorbed Fe 3+ showed an important activity in the oxidation process, although smaller than octahedral Fe 3+. The kinetics of oxidative degradation of hydrocortisone by palygorskite appear to be composed of two apparent first order reactions which may be associated with two kinds of sites for Fe in palygorskite. The lower oxidizing power of sepiolite for hydrocortisone degradation is due to its very low Fe z+ content.

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“…The biological half-life of the deuterated drug was about 2.5 times longer than the non-deuterated. Pitman et al [6] synthesized hydrocortisone in which two deuterium atoms were incorporated in the C21 position. Under oxidative conditions, the deuterated compound was more stable than the non-deuterated form.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Plasma Concentration by Selective Deuteration of Rofecoxib in Rats

Schneider¹,

Hillgenberg²,

Koytchev

et al. 2011

Arzneimittelforschung

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The plasma concentrations of BDD-11602 (4-[4- (methanesulfonyl)phenyl]-3-(pentadeuterophenyl)-5H-furan-2-one), a rofecoxib derivative in which the positions 2',3;4',5' and 6' of the phenyl ring were deuterated, and rofecoxib (4-(4-methylsulfonylphenyl)-3-phenyl-5H-furan-2-one, CAS 162011-90-7) were compared in order to explore the effects of selective deuteration on the systemic availability. The COX-2 selectivity in vitro was also compared. Following oral gavage administration of 0.1, 1 or 10 mg/kg BDD-11602 to Sprague Dawley rats, AUCo-t, (area under the curve) and Cmax (maximum concentration) values were statistically significant higher than those of rofecoxib at the same doses. The overall increase in AUC0-t and Cmax for BDD-11602 over rofecoxib was 1.53-fold and 1.60-fold, respectively. BDD-11602 and rofecoxib inhibited COX-2-derived PGE(2) synthesis with IC50 values of 173 nmol/l and 169 nmol/l, respectively. IC50 values for inhibition of human platelet COX-1 were estimated to be above 1 micromol/l for both compounds. The substitution of hydrogen by deuterium on the positions 2: 3',4',5' and 6' in BDD-11602 leads to superior oral availability compared to the non-deuterated compound, whereas the COX-2 selectivity is not affected.

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Deuterium Isotope Effects on Degradation of Hydrocortisone in Aqueous Solution

Cited by 13 publications

References 6 publications

Studies with Deuterated Drugs

Studies with Deuterated Drugs

Role of Ferric Iron in the Oxidation of Hydrocortisone by Sepiolite and Palygorskite

Enhanced Plasma Concentration by Selective Deuteration of Rofecoxib in Rats

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