Daily Rhythms in the Hydroxylation of 3<i>β</i>-Hydroxyandrost-5-en-17-one by Rat Liver Microsomes

Colás, A.E.; Gregonis, D. E.; Moir, Neil J.

doi:10.1210/endo-84-1-165

Cited by 25 publications

(2 citation statements)

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“…Several hepatic-metabolizing enzymes, including cholesterol 17α-hydroxylase (maximum 0200, minimum 0800-1200 h), 6 3-β-hydroxy androst-5-en-17-one-7α-hydroxylase (maximum 0200, minimum 1000 h), 7 aminopyrine N-demethylase [(maximum 0200-1000, minimum 0600 h), 8 (maximum 1800, minimum 0600 h), 9 (maximum 2000, minimum 1000 h) 7 ], benzpyrene hydroxylase (maximum 1800, minimum 0600 h), 9 cytochrome P-450 (maximum 2200, minimum 1000 h), 10 and cytochrome P-450 reductase (maximum 0000, minimum 1424 h), 10 including P-450 mixed-function oxidase system and P-450 monooxygenase system, have been reported to exhibit time-dependent variations. Although DEC is metabolized to a considerable extent in laboratory animals, about 62% is excreted unchanged and 10% excreted as an N-oxide metabolite in humans.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Diethylcarbamazine after Single Oral Dose at Two Different Times of Day in Human Subjects

Bolla¹,

Boinpally²,

Poondru³

et al. 2002

The Journal of Clinical Pharma

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In most Wuchereria bancrofti and Brugia malayi infections, the microfilaria are found in the blood in greatest number between 10 p.m. and 2 a.m., indicating that chronotherapy may be beneficial in treating such infections. This study reports the influence of time of administration on the pharmacokinetics of diethylcarbamazine (DEC) in healthy volunteers. The study was conducted in 12 healthy volunteers by administering a 150 mg single oral dose of diethylcarbamazine citrate at 0600 or 1800 h in a balanced crossover design with the approval of an institutional ethics committee. The subjects fasted for about 10 hours before and 3 hours after drug treatment. Blood samples were collected at predetermined time intervals, and the drug content in the serum was estimated using HPLC with an electrochemical detector. Pharmacokinetic analysis was performed using noncompartmental methods employing WinNonlin (version 3.1), and the means of various pharmacokinetic parameters were compared for any dosing time-related changes using a paired t-test at a probability level of 95%. The mean +/- SD values of pharmacokinetic parameters of DEC for the treatments at 0600 versus 1800 h were as follows: Cmax, 500+/-227 versus 637+/-401 ng/ml; tmax, 2.3+/-0.7 versus 2.7+/-1 h; Ka, 2.23+/-0.72 versus 1.96+/-0.97 h(-1); t1/2, 14.6+/-6.7 versus 11.4+/-4.9 h; AUC0-t, 5,334+/-1,853 versus 6,901+/-4,203 ng x h/ml; AUC0-infinity, 5,840+/-1,922 versus 7,220+/-4,205 ng x h/ml; CL/F, 36,058+/-19,011 versus 32,189+/-25,293 ml/h/kg; Vd/F, 570+/-225 versus 533+/-447 L; and MRT 17.7+/-5.9 versus 15.3+/-5.2 h. None of the parameters was significantly changed (p > 0.05) as a function of time of administration.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Diethylcarbamazine after Single Oral Dose at Two Different Times of Day in Human Subjects

Bolla¹,

Boinpally²,

Poondru³

et al. 2002

The Journal of Clinical Pharma

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“…Several natural steroids are 7a-hydroxylated in the living organism prior to being excreted mainly in the urine. This is the case for testosterone [30,31], dehydroepiandrosterone [32,33] and pregnenolone [34]. However, some basic biochemical properties, like apparent Fig.…”

Section: Action Of Various Steroidsmentioning

confidence: 99%

Cholesterol 7 α‐Hydroxylase

Cantfort

Gielen

1975

European Journal of Biochemistry

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70% of the microsome‐bound cholesterol is directly accessible to cholesterol 7α‐hydroxylase in an assay in vitro. After 5 min of incubation this endogenous cholesterol makes a single pool with the exogenously added substrate and modifies its specific radioactivity. Thus, an accurate estimation of the enzymic activity should take the participation of endogenous cholesterol into account. Cholesterol 7α‐hydroxylase activity is enhanced in vitro by thiol‐containing substances like mercaptoethanol, dithiothreitol, or cysteamine. On the contrary, the enzymic activity is inhibited by heavy cations (Hg2+, Pb2+, Cu2+, Zn2+), or −SH‐blocking agents (mersalic acid, p‐chloro‐mercuribenzoic acid). Several steroids are potent inhibitors (Ki < Km) of the enzyme, among them pregnenolone and its acetate derivative and the cholesterol closely related 7‐oxocholesterol and 7‐dehydrocholesterol. The cholesterol esters are neither substrates nor inhibitors of cholesterol 7α‐hydroxylase. Only a high concentration (1 mM) of biliary acids or of their glyco or tauro derivatives inhibits cholesterol 7α‐hydroxylase. The quantitatively less important lithocholic acid and deoxycholic acid are the strongest inhibitors; the most common cholic acid does not affect the enzymic activity even at 1 mM.

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Chronopharmacokinetics of Ethanol

Sturtevant¹,

Sturtevant²

1979

Biochemistry and Pharmacology of Ethanol

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Daily Rhythms in the Hydroxylation of 3β-Hydroxyandrost-5-en-17-one by Rat Liver Microsomes

Cited by 25 publications

References 0 publications

Pharmacokinetics of Diethylcarbamazine after Single Oral Dose at Two Different Times of Day in Human Subjects

Pharmacokinetics of Diethylcarbamazine after Single Oral Dose at Two Different Times of Day in Human Subjects

Cholesterol 7 α‐Hydroxylase

Chronopharmacokinetics of Ethanol

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