Drug management of hypercholesterolemia

Martz, B. L.

doi:10.1016/0002-8703(79)90441-1

Cited by 16 publications

(3 citation statements)

References 82 publications

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“…. e 1 k2 (ki-kz) (4) Pharmacokinetic analysis was performed using the mean data from the postprandial I4C and 3H subject groups simultaneously, thus providing the same effect as if dual labelled DMPP were administered. For parent drug levels in blood and feces, the average data from the two subject groups were used.…”

Section: -Kri (T-lt-rt) Ar (12f) O[l-e -K2 (T-lt-rt)mentioning

confidence: 99%

Disposition of a silicon‐containing amide, an inhibitor of acyl‐CoA: Cholesterol acyltransferase, in dog and rat

Tse¹,

Jaffe²

1987

Biopharm & Drug Disp

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The pharmacokinetics of 3-(decyldimethylsilyl)-N-[2-(4-methylphenyl)-1-phenylethyl]propanamide (DMPP), an inhibitor of acyl-CoA:cholesterol acyltransferase, have been studied in the dog and the rat using 14C and 3H dual-labelled drug. In both species, gastrointestinal absorption of DMPP was slow and incomplete, amounting to approximately 20 per cent of the oral dose given in corn oil. In the rat, use of PEG-400, Tween 80, ethanol, and aqueous CMC as vehicles resulted in similar or lower absorption than corn oil. Absorbed DMPP was rapidly and extensively distributed to body tissues. Data from the rat showed highest concentrations of radioactivity in the liver and spleen, while concentrations in the adrenals and lung also markedly exceeded circulating radioactivity levels. In both dog and rat. DMPP was completely metabolized prior to excretion. The routes of biotransformation involved hydrolysis of the amide bond, oxidation of the phenyl ring, and degradation of the decyldimethylsilyl propanoyl moiety. The metabolites of DMPP were excreted slowly, predominantly in the faeces. The elimination half-life of 14C was 105 h in the dog and 83 h in the rat, while that of 3H was approximately 32 h in both species.

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Section: -Kri (T-lt-rt) Ar (12f) O[l-e -K2 (T-lt-rt)mentioning

confidence: 99%

Disposition of a silicon‐containing amide, an inhibitor of acyl‐CoA: Cholesterol acyltransferase, in dog and rat

Tse¹,

Jaffe²

1987

Biopharm & Drug Disp

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show abstract

“…octanol: water coefficient using Hans& analysis being grade and were used without further purificavariable (Martz 1979), though' improved by the presence of food. Administration of a single oral dose to man gives peak plasma concentrations after 24 h and elimination is biphasic with half-lives of approximately 1 and 23 days (Heeg & Tachizawa 1980).…”

mentioning

confidence: 99%

“…During chronic administration, the plasma concentration of probucol gradually rises reaching a stready state after 2 4 months. After discontinuance of the drug, elimination is slow with 60% of the original plasma concentration remaining after 6 weeks (Martz 1979). This characteristic slow rise and fall in plasma values is due to the storage of the drug within body adipose tissue (Heel et a1 1978).…”

mentioning

confidence: 99%

The effect of different oils on the absorption of probucol in the rat

Palin

Wilson

1984

Journal of Pharmacy and Pharmacology

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The effect of oily vehicles on the gastrointestinal absorption of the hypocholesterolaemic agent probucol has been investigated in the rat. The plasma concentration was determined following its administration in arachis oil (peanut oil), Miglyol 812 (fractionated coconut oil) and liquid paraffin. The total absorption of the drug, calculated as the area under the plasma concentration time curve, was significantly greater for the arachis oil formulation than with the other vehicles. The drug was selectively absorbed via the lymphatic system, lymph drug concentrations being highest following co-administration of arachis oil.

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Influence of high‐fat meal on the absorption of a silicon — containing amide, an inhibitor of acyl — coa: Cholesterol acyltransferase, in man

Tse¹,

Jaffe²

1988

Biopharm & Drug Disp

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The pharmacokinetics of 3-(decyldimethylsilyl)-N-[2-(4-methylphenyl)-1- phenylethyl] propanamide (DMPP), an inhibitor of acyl-CoA: cholesterol acyltransferase, have been examined in 18 healthy male volunteers who received an oral dose of either 14C-DMPP or 3H-DMPP immediately following a high-fat meal, or 3H-DMPP in the fasting state. DMPP was poorly absorbed in the fasting subjects. Administration with a high-fat meal significantly increased the extent of absorption to 15 per cent of the dose. Simultaneous fitting of the blood levels and excretion data to a pharmacokinetic model showed that ca. 64 per cent of the absorbed DMPP was metabolized while the remainder was excreted intact via the bile. The routes of biotransformation included hydrolysis of the amide bond and oxidation of the phenyl ring. The apparent volumes of distribution for DMPP and its 14C and 3H labelled metabolites were 0.89, 0.95, and 1.6 lkg-1, respectively, suggesting that these materials were distributed into extravascular spaces. The metabolites of DMPP were partially excreted in urine, accounting for 1.2 per cent and 3.8 per cent of the postprandial 14C and 3H labelled doses, respectively. The elimination half-lives of DMPP and its 14C and 3H labelled metabolites were 2.8, 5.3, and 6.9 h, respectively.

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Drug management of hypercholesterolemia

Cited by 16 publications

References 82 publications

Disposition of a silicon‐containing amide, an inhibitor of acyl‐CoA: Cholesterol acyltransferase, in dog and rat

Disposition of a silicon‐containing amide, an inhibitor of acyl‐CoA: Cholesterol acyltransferase, in dog and rat

The effect of different oils on the absorption of probucol in the rat

Influence of high‐fat meal on the absorption of a silicon — containing amide, an inhibitor of acyl — coa: Cholesterol acyltransferase, in man

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