Biomedical subjects

A Rautio

Publications and source records attributed to A Rautio.

46 records · Page 3Linked to original sources

PubMed1985

Effects of high dose progestin on serum lipids and lipid metabolizing enzymes in patients with endometrial cancer.

The effect of high dose medroxyprogesterone acetate (MPA) on serum lipids, on adipose tissue lipoprotein lipase (LPL) and serum lecithin cholesterol acyltransferase activities were studied in 15 postmenopausal patients with endometrial cancer. After 2 weeks of MPA treatment total cholesterol decreased by 14% (P less than 0.001) and HDL cholesterol by 33% (P less than 0.01) from the respective pretreatment values; correspondingly the ratio of HDL to total cholesterol decreased (P less than 0.05). The decrease of HDL2 cholesterol was 35% (P less than 0.01) and that of HDL3 cholesterol 15% (P less than 0.01). The levels of serum triglycerides decreased significantly (P less than 0.05) during the treatment period. Serum LCAT activity was significantly lower (P less than 0.05) after treatment than before, but adipose tissue LPL activity was not altered. The mean serum testosterone level decreased significantly (P less than 0.001) from the pretreatment values. Significant positive correlations were present between LPL activity and MPA concentrations and between LPL activity and testosterone concentrations after the drug treatment.

Adipose Tissue↗

PubMed1985

Metabolism of medroxyprogesterone acetate and hepatic drug metabolism activity.

The effect of microsomal enzyme activity on the hepatic metabolism of medroxyprogesterone acetate (MPA), measured in vitro, and the MPA concentrations in liver and plasma were investigated in rats with intact and injured livers before and after MPA therapy. The amount of total MPA metabolites and the activity of drug-metabolizing enzyme system changed in a parallel manner in the livers. The ratio of liver/plasma concentration of MPA was decreased in the liver injury. The hepatic metabolism of MPA is accelerated during MPA treatment in rat.

Animals↗

PubMed1984

Liver function and medroxyprogesterone acetate elimination in man.

Medroxyprogesterone acetate (MPA) elimination rate was investigated in 25 patients with primary biliary cirrhosis, alcoholic cirrhosis and fatty liver. The serum and urine concentrations of MPA were measured by RIA after a single oral administration of the drug. Biochemical liver tests and antipyrine kinetics were determined as indicators of the liver function. The antipyrine test, a reflector of the activity of hepatic drug-metabolizing enzyme system, was impaired only in alcoholics. The results demonstrate that the elimination rate of MPA is reduced in subjects with alcoholic cirrhosis, whereas the values of the patients with fatty liver and primary biliary cirrhosis are in the normal range. The findings show that the MPA elimination is impaired only in cases with far advanced liver disease.

Antipyrine↗

PubMed1983

Disposition of medroxyprogesterone acetate and drug metabolism activity.

The role of drug-metabolizing enzyme activity on the disposition of medroxyprogesterone acetate (MPA) was investigated in male rats. The metabolizing enzyme system was induced by phenobarbital (PB) or inhibited by SKF 525A. Plasma concentrations of unmetabolized MPA and the amounts of MPA-related residues in various tissues were higher in the SKF 525A and slightly lower in the PB treated animals than in the controls. The disappearance of MPA-related substances from the lung, skeletal muscle and brain was slow, and in the lung there was even an increase in the amount of radioactivity in the PB and saline treated rats at 24 hr. Almost equal amounts of radioactivity were excreted in the urine and intestine in the control rats, while the induction of drug metabolism enhanced the excretion in the urine and its reduction enhanced elimination in the intestinal tract within 24 hours. The findings demonstrate that plasma and tissue levels of MPA and its elimination route are influenced by the drug metabolism activity.

Animals↗

PubMed1982

Pericellular collagen in alcoholics with liver cirrhosis.

Therapy with enzyme inducing drugs may improve the clinical state of alcoholics with liver cirrhosis. The histological changes associated with the therapy were investigated by comparing liver biopsies before and after phenobarbital and medroxyprogesterone acetate treatment, known inducers of hepatic microsomal enzyme system, in eight alcoholics with cirrhosis and two control groups, subjects with normal liver and endstage alcoholic cirrhosis. Pericellular collagen, determined morphometrically, reduced from a point value of 87.6 +/- 28.3 to 63.4 +/- 16.7 (p less than 0.01), while the fibrous septa as well as the non-fatty and fatty parenchyma did not alter significantly. Antipyrine metabolism, an index of hepatic cell function, improved from 17.4 +/- 6.4 to 45.6 +/- 22.2 ml/min (p less than 0.01). Although direct correlation between the decrease of pericellular collagen fibres and antipyrine metabolism was not significant (r = 0.410) the findings suggest that accumulation of pericellular collagen prevents mechanically and availability of the compound to the cell, thus delaying its metabolism.

Adult↗

PubMed1981

Propranolol and sotalol metabolism after a drinking party.

The effects of alcohol consumed during an evening party on the metabolism and response of beta-adrenergic blocking drugs were investigated in healthy subjects. The drugs were given 12 hr after the first drink. The plasma clearance rate of propranolol, metabolized in the liver, increased, while that of sotalol, which is eliminated unchanged, was reduced. Plasma propranolol levels, but not those of sotalol, were related to blood alcohol content. The blood pressure-reducing effect of propranolol diminished after alcohol and that of sotalol increased. Both drugs reduced the heart rate after alcohol although they were unable to cancel out entirely the alcohol-induced increase in the heart rate. The results show that drinking may alter the metabolism of beta-blocking drugs. Drinking habits must be considered in therapy with beta-blocking drugs or when seeking reasons for angina pectoris or arterial hypertension that does not respond to therapy.

Adult↗

PubMed1980

Treatment of alcoholic cirrhosis with enzyme inducers.

The efficacy of hepatic enzyme-inducing drugs in improving liver function and drug metabolism was investigated in 18 chronic alcoholics with cirrhosis. Five subjects treated continuously with the inducing drugs, phenytoin or prednisolone, for concomitant diseases showed more rapid metabolism than the other patients. Phenobarbital (PB) and medroxyprogesterone acetate (MPA), both known inducers, improved drug metabolism in patients with normal or decreased serum albumin. Serum albumin levels rose in alcoholics with low pretherapy levels, whereas serum albumin in subjects with normal pretherapy levels did not change. Serum thrombotest levels rose in six of seven subjects with low pretreatment values. There was a trend toward normal conventional liver tests during the experiment. There was a relationship between in vivo and in vitro drug metabolism in the alcoholics with cirrhosis. Our results demonstrate that by activating liver function, enzyme-inducing drugs may be of therapeutic value in alcoholics with liver cirrhosis and hepatic failure.

Adult↗

PubMed1979

Antipyrine metabolism and liver function in patients treated with high-dose medroxyprogesterone.

The effect of high-dose medroxyprogesterone acetate (MPA, 250 mg intramuscularly for six days) on hepatic drug-metabolism and liver function was investigated in eleven females with endometrial carcinoma. Antipyrine plasma clearance, an index of hepatic drug-metabolizing ability, improved significantly during this treatment, and the serum total bilirubin level was lowered, whereas other liver function tests, including alkaline phosphatase, and albumin values in the serum, remained unchanged. The results demonstrate that therapy with MPA has an inducing effect on hepatic enzyme activity and antipyrine metabolism. The findings may be of importance when prescribing drugs for females receiving large doses of MPA.

Adult↗

PubMedDate not supplied

Liver enzyme induction and serum lipid levels after replacement of carbamazepine with oxcarbazepine.

We evaluated liver P450 enzyme system induction and serum lipid levels in a prospective follow-up study in 12 male patients with epilepsy after replacing carbamazepine (CBZ) medication with oxcarbazepine (OCBZ). Antipyrine(t1/2) increased and antipyrine(CL) decreased 2 months after the medication was changed, reflecting normalization of liver P450 enzyme system function. Furthermore, serum total cholesterol levels decreased, but serum concentrations of high-density lipoprotein (HDL)-cholesterol and triglycerides (TG) were unchanged. OCBZ may be the preferable antiepileptic drug (AED) with regard to the effects of the medication on lipid metabolism.

Adult↗

PubMedDate not supplied

Age and CYP3A4 and CYP2A6 activities marked by the metabolism of lignocaine and coumarin in man.

The effect of age on human liver drug-metabolizing ability was investigated by using probe drugs, metabolized by specific isozymes in liver, as an index. Formation of monoethylglycinexylide (MEGX) after i.v. infusion of lignocaine (1 mg/kg), metabolized by CYP3A4, and excretion of 7-hydroxycoumarin (7-OHC) after oral coumarin (5 mg) administration, hydroxylated by CYP2A6, were investigated in healthy young (< 25 years) and elderly (> 65 years) women and men (n = 10 in each group). MEGX content in young subjects (men 57.8 +/- 11.3 and women 52.9 +/- 13.1 ng/ml) did not diverge significantly but was reduced in elderly subjects (men 43.57 +/- 15.8 and women 29.2 +/- 13.6 ng/ml, p < 0.05 and 0.01, respectively). 7-OHC excretion at 2 h averaged 68.1 +/- 13.1 per cent (men) and 65.0 +/- 18.3 per cent (women) of the dose given in young subjects and was delayed in elderly persons (men 46.5 +/- 16.3 per cent and women 44.8 +/- 18.3 percent, p < 0.01 and 0.05, respectively). The change in probe drug metabolism was related to age (MEGX, r = -0.473 (men) and -0.682 (women) and 7-OHC; r = -0.690 (men) and -0.565 (women)). MEGX formation was reduced by 0.92 microgram/L per year and 7-OHC excretion by 0.85 per cent per year. The results indicate a decrease of CYP3A4 and CYP2A6 metabolic activities with age.

Adult↗