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Biomedical subjects

E A Sotaniemi

Publications and source records attributed to E A Sotaniemi.

At least 19 recordsLinked to original sources
PubMed1997

Hepatitis A impairs the function of human hepatic CYP2A6 in vivo.

Hepatitis virus A (HVA) is a worldwide sporadic disease but its effects on pharmacokinetics and individual drug responses have not been studied. In this study, the 7-hydroxycoumarin (7OHC) excretion test used in vivo as a bioindex of hepatic CYP2A6 activity was performed in 20, previously healthy, acute jaundice HVA patients. Volunteers with an acute HVA were treated with one p.o. administration of 5 mg coumarin (Venalot). Among the patients, 11 were children (6-10 years; two girls and nine boys), the rest (15-40 years old) consisted of two men and seven women. Urinary excretion of 7OHC was measured after overnight fasting in four fractions: 0 h before any medication (to detect if any basal 7OHC excretion exits), and after a 5-mg coumarin capsule p.o., 0-2, 2-4 and 4-8 h fractions were collected and urine volumes were recorded. Urinary excretion of 7-hydroxycoumarin occurred to a similar extent in healthy adults and children. The first 2-h 7OHC excretion was decreased by 26% (P < 0.05) and total (0-8 h) 7OHC excretion was decreased by 37% (P<0.01) among HVA-positive adults (age range 15-40 years) compared with the values obtained from healthy volunteers. In 11 HVA-positive children (age 6-10 years), the first 2-h 7OHC excretion was only 20% (P < 0.0001) and the total 7OHC excretion 28% (P < 0.0001) of the value observed in healthy controls. These results suggest that (i) an acute HVA decreases the metabolic clearance of drugs such as coumarin which are rapidly metabolised by CYP2A6 and (ii) this decrease is even more prominent in children. Such metabolic responses may be of clinical importance and may also interfere with other drug therapy in these patients.

Adolescent↗
PubMed1997

Influence of age on toremifene pharmacokinetics.

Toremifene pharmacokinetics were compared in ten healthy young men (< 33 years) and elderly women (< 65 years). A single oral 120-mg dose of toremifene was given after an overnight fast and blood samples were collected over 28 days. Serum levels of the parent drug and the metabolites were determined; appropriate pharmacokinetic parameters were calculated and statistically evaluated. Toremifene peak concentrations (average 640 ng/ml) were achieved at 3.5 h. The area under the curve (AUC) and the apparent oral clearance were comparable in the young and elderly subjects. The half-life was prolonged (4.2 versus 7.2 days) and the apparent volume of distribution was increased (457 versus 627 1) in the elderly. The peak concentration of the main metabolite N-demethyltoremifene was lower (159 versus 233 ng/ml) and the half-life was prolonged (8.3 versus 19.1 days) in the elderly subjects, but the AUC values were comparable. The results suggest that toremifene is distributed more widely in the elderly but that its clearance is unaffected by age. It is concluded that the dosage requirement of the drug is unlikely to differ between young and elderly subjects.

Adult↗
PubMed1997

Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions.

OBJECTIVES: The effect of aging on drug metabolism in humans has not yet been completely described. METHODS: Two hundred twenty-six patients with equal histopathologic conditions were investigated. The cytochrome P450 contents in the liver biopsy samples, the plasma antipyrine clearance rates after oral administration and, as an independent control of vitality, serum testosterone levels were determined. RESULTS: Cytochrome P450 content in subjects from 20 to 29 years of age was 7.2 +/- 2.6 nmol.gm-1, increased during the fourth decade (+7.2%, p = NS), declined after 40 years (-16%, p < 0.01) to a level that remained unaltered up to 69 years, and declined further after 70 years (-32%, p < 0.001). The antipyrine (phenazone) clearance rate in young subjects was 46.4 +/- 18.5 ml.min-1, remained unaltered during the fourth decade, and declined after 40 years by a rate of 0.34 ml.min-1 per year toward old age (-29%, p < 0.001). The half-life in young subjects was 9.5 +/- 2.0 hours and increased after 30 years toward old age (+26%, p < 0.001). The volume of antipyrine distribution, 0.46 +/- 0.12 L.kg-1 in young subjects, decreased after 30 years (-11%). In line with the testosterone content, the decrease in drug metabolism was equal in both sexes. CONCLUSION: This study shows a reduction of in vitro and in vivo drug metabolism with age in humans. The data suggest that at least three age groups--young, middle-aged, and elderly--should be included in the evaluation of the pharmacokinetics of a new drug. The reduction of drug metabolism (-30%) after 70 years of age indicates that care is needed in the prescription of drugs for elderly subjects.

Adult↗
PubMed1996

Iron deficiency anemia, backache, and abdominal pain attacks during sexual intercourse in a 42-year-old woman.

BACKGROUND: Gastrointestinal bleeding is a common diagnostic problem. We describe here a 42-year-old woman who had iron deficiency anemia that went undiagnosed for 8 years. SYMPTOMS AND RESULTS: She had a 'blood spray' when crouching, backache, and abdominal pain attacks during sexual intercourse. Defecography, but neither clinical examination nor endoscopy, demonstrated abnormal mobility of the rectal mucosa associated with other pelvic floor abnormalities. THERAPY: After rectopexy, the bleeding stopped, and the blood values normalized.

Abdominal Pain↗
PubMed1995

Pharmacokinetics of the novel antiestrogenic agent toremifene in subjects with altered liver and kidney function.

OBJECTIVES: The pharmacokinetics of toremifene was investigated in an open study with four parallel groups of 10 subjects each. Subjects with impaired liver function (biopsy-proven liver disease), activated liver function (drug-induced), and impaired kidney function were compared with normal subjects. METHODS: A single oral 120 mg dose of toremifene was administered after an overnight fast, and blood samples were collected over 28 days. Serum levels of toremifene and its metabolites were determined; appropriate pharmacokinetic parameters were calculated and statistically evaluated. RESULTS: In normal subjects, the average peak level of 414 ng/ml toremifene was achieved at 3 hours after dosing, the terminal half-life was 6.2 days, apparent oral clearance was 5.1 L/hr, apparent volume of distribution was 958 L, and the fraction not bound to protein was 0.3%. The peak level (130 ng/ml) of the major metabolite, N-demethyltoremifene, appeared in serum with large variation in the time to peak level (median, 3 days) and a terminal half-life of 21.0 days. Low levels of deaminohydroxytoremifene were also measured, and two other metabolites could be quantified at some time points in some patients. The elimination rate of toremifene and the main metabolite was significantly increased in patients with activated liver function, resulting in decreased terminal half-lives (3.0 days and 4.5 days, respectively), and was decreased in patients with impaired liver function (10.9 days and 29.6 days, respectively). The subjects with impaired kidney function showed normal elimination kinetics. CONCLUSION: Liver, but not kidney, function should be taken into account when toremifene is administered.

Administration, Oral↗
PubMed1995

Antipyrine, coumarin and glipizide affect n-acetylation measured by caffeine test.

The effect of various treatments on acetylation status measured by caffeine metabolites was investigated in 17 subjects with non-insulin dependent diabetes mellitus (NIDDM). The test drugs, caffeine (200 mg), antipyrine (20 mg/kg) and coumarin (5 mg), were given simultaneously, and urinary 5-acetylamino-6-formyl-amino-3-methyluracil/1-methylxanthine (AFMU/1X) molar ratio was measured before and after 8 weeks of therapy. The urinary AFMU/1X molar ratio decreased (p < 0.05) after 8 weeks of therapy with glipizide (2.5 mg), but remained unaltered in those treated with placebo or those who self-monitored blood glucose (SMBG) by glucometer. Antipyrine and coumarin decreased (p < 0.05) the AFMU/1X molar ratio both in diabetics and healthy volunteers. Our data demonstrate that glipizide, antipyrine and coumarin may interfere with the classification of acetylator status measured by caffeine metabolites.

Acetylation↗
PubMed1995

CYP3A4 and CYP2A6 activities marked by the metabolism of lignocaine and coumarin in patients with liver and kidney diseases and epileptic patients.

1. The in vitro hepatic metabolism of lignocaine to monoethylglycinexylide (MEGX) is mediated by CYP3A4 and that of coumarin to 7-hydroxycoumarin (7OHC) by CYP2A6. We investigated the usefulness of monitoring serum MEGX concentrations (after 1 mg kg-1 lignocaine i.v.) and urinary 7OHC excretion (after 5 mg coumarin p.o.) to reflect liver function in patients with liver (n = 36), kidney (n = 12) and epileptic (n = 12) disease and in control subjects (n = 20). The extent of liver disease was assessed using measurements of serum aminoterminal propeptide (PIIINP) and Child-Pugh grades. 2. Serum concentrations of MEGX were decreased in severe (4.6 +/- 3.0 s.d. ng ml-1), moderate (19.1 +/- 11.6 s.d. ng ml-1) and mild (32.8 +/- 14.2 s.d ng ml-1) liver disease as compared with controls (53.4 +/- 15.8 s.d ng ml-1). The excretion of 7OHC over 2 h was decreased in severe (18.0 +/- 10.3 s.d % of dose) and moderate (34.2 +/- 15.6 s.d %), but not in mild (49.7 +/- 19.0 s.d %) liver disease as compared with that in controls (56.2 +/- 11.6%). 3. In epileptic patients the urinary recovery of 7OHC was increased (2 h value 69.5 +/- 13.2 s.d %) suggesting enzyme induction. In contrast, serum MEGX concentration were low (40.0 +/- 14.1 s.d ng ml-1), possibly due to competition for CYP3A4 between lignocaine and antiepileptic drugs. 4. In patients with kidney disease serum MEGX concentration (56.5 +/- 26.1 s.d ng ml-1) was similar to that in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Ginseng therapy in non-insulin-dependent diabetic patients.

OBJECTIVE: To investigate the effect of ginseng on newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients. RESEARCH DESIGN AND METHODS: In this double-blind placebo-controlled study, 36 NIDDM patients were treated for 8 weeks with ginseng (100 or 200 mg) or placebo. Efficacy was evaluated with psychophysical tests and measurements of glucose balance, serum lipids, aminoterminalpropeptide (PIIINP) concentration, and body weight. RESULTS: Ginseng therapy elevated mood, improved psychophysical performance, and reduced fasting blood glucose (FBG) and body weight. The 200-mg dose of ginseng improved glycated hemoglobin, serum PIIINP, and physical activity. Placebo reduced body weight and altered the serum lipid profile but did not alter FBG. CONCLUSIONS: Ginseng may be a useful therapeutic adjunct in the management of NIDDM.

Affect↗
PubMed1993

The pharmacokinetics of Casodex enantiomers in subjects with impaired liver function.

1. Casodex is a novel non-steroidal antiandrogen being developed for the treatment of prostatic cancer. The antiandrogenic activity is predominantly in the R(-) enantiomer with little, if any, activity in the S(+) enantiomer. 2. The pharmacokinetics of the enantiomers of Casodex have been investigated over 28 days following a single oral dose of Casodex (50 mg) to 10 male subjects with histologically verified liver cirrhosis or fatty liver with fibrosis. Ten age matched male subjects with normal hepatic function served as a control group. 3. For both groups plasma concentrations of (S)-Casodex were lower than those for (R)-Casodex; this difference was about 10-fold at early time points and increased to about 25-fold by 24 h after dosage. 4. The kinetics of (R)-Casodex were similar in subjects with and without liver disease (Cmax: 750 vs 848 ng ml(-1); tmax: 24 - 30 h; t(1/2): 7.40 vs 7.22 days; AUC: 182 vs 225 microg ml(-1) h). 5. The kinetics of (S)-Casodex could not be described in the majority of subjects; in the remainder the mean terminal phase half-life for both groups was less than 1 day.

Androgen Antagonists↗
PubMed1992

Effect of insulin on serum amino-terminal propeptide of type III procollagen in non-insulin-dependent diabetes mellitus.

The effect of insulin on the serum levels of the amino-terminal propeptide of type III procollagen (PIIINP) was investigated in patients with non-insulin-dependent diabetes mellitus, whose disease was unsatisfactorily controlled by oral drugs. Before insulin therapy the PIIINP values of the patients (3.2 +/- 1.3 micrograms/l, n = 38) varied within the range of healthy subjects (3.1 +/- 0.6 micrograms/l, n = 50, NS). Insulin therapy (6-20 IU at bedtime plus the oral drugs) improved the glycemic control and increased the serum PIIINP during a 4 week (3.1 +/- 0.9 to 3.8 +/- 1.1 micrograms/l, P less than 0.01, n = 8) and an 8 week period (3.2 +/- 1.3 to 3.8 +/- 1.6 micrograms/l, P less than 0.001, n = 22). The values were still elevated after 6 months on insulin (3.5 +/- 1.5 to 4.0 +/- 1.7 micrograms/l, P less than 0.01, n = 12). Placebo-insulin did not alter the concentration of PIIINP (3.1 +/- 0.6 to 2.8 +/- 0.6 micrograms/l, NS, n = 8) whereas the glycemic control improved and body weight decreased. The PIIINP values correlated with fasting insulin before (r = 0.403, P less than 0.05, n = 30) and after the therapy (r = 0.452, P less than 0.001, n = 60). Insulin therapy, while correcting the hormone deficiency and restoring glucose and protein metabolism, seems to activate the synthesis of type III procollagen in patients with NIDDM. This may promote the atherosclerotic process.

Adult↗
PubMed1991

Time dependent effects of medroxyprogesterone acetate on hepatic ultrastructure in rats.

The present study demonstrates that MPA treatment may alter liver ultrastructure in rats. This was seen as a slight cytoplasmic vacuolization in light microscopy. In electron microscopy the most striking findings were the increase in the size of hepatocytes, the volume of smooth endoplasmic reticulum (SER) and the number of mitochondria. Minor changes in mitochondrial size and structure, and SER outline were also obtained. The amount of rough endoplasmic reticulum was decreased and bleb formation was common. The effect of MPA on liver ultrastructure was time-dependent. The main changes were found in rats receiving MPA daily for seven days. Most of the observed changes disappeared within 17 days after the cessation of the regimen. MPA induced alterations in liver morphology may partly be due to induction phenomenon although the hormonal property of MPA also may play some etiological role.

Animals↗
PubMed1990

High-density lipoprotein subfractions, apolipoproteins and antipyrine clearance in normal subjects.

Serum high density lipoprotein (HDL) subfractions HDL2 and HDL3, apolipoproteins, and plasma antipyrine clearance (AP-CL) rate, an index of liver microsomal enzyme activity, were determined in 21 healthy subjects. High HDL cholesterol and HDL2 cholesterol concentrations and HDL cholesterol/cholesterol and HDL2/HDL3 cholesterol ratios were associated with high AP-CL. Phenobarbital enhanced antipyrine elimination and increased the apolipoprotein A-I/A-II ratio. Subjects who had high AP-CL had a more antiatherogenic HDL subfraction and apolipoprotein profile than those with low AP-CL.

Adult↗
PubMed1990

Insulin and sulphonylurea in the therapy of type 2 diabetes.

The role of insulin in the therapy of NIDDM is still under discussion. To clarify the problem we performed a randomized double-blind placebo controlled crossover study of insulin treatment for 4 weeks in diabetic patients (n = 18, age 52-74 years) who were unsatisfactorily controlled by oral antidiabetic agents. The patients continued to use these agents during the study. Special attention was given to informing the patients about the trial and, in particular, about self-monitoring the blood glucose by the use of a reflectance meter. Insulin treatment produced the following significant changes: decreases in blood glucose (at 7.00, 10.00, 16.00), mean daily blood glucose, HbA1, urinary glucose and low density lipoprotein (LDL) cholesterol and increased postglucose immunoreactive insulin (IRI) levels. Significant changes were also observed during the placebo periods: decreases in HbA1 urinary glucose and LDL cholesterol (but not in blood glucose). Therapy with insulin increased the body weight, whereas the placebo insulin had the opposite effect. The finding emphasizes the importance of using not only a run-in period but also a placebo design when the metabolic effects of antidiabetes therapy are to be evaluated. The study indicates that insulin therapy for patients with type 2 diabetes can be initiated at home.

Aged↗
PubMed1990

Reduced glucose-6-phosphorylase and NADPH generating enzyme activities associated with glibenclamide induced hypoglycemia and hypoinsulinemia in genetically obese mice.

Addition of phenobarbital, an inducer of the liver mixed function oxidase system, to sulphonylurea regimen improves insulin sensitivity and intracellular glucose handling in patients with non-insulin dependent diabetes mellitus. The inducer also activates liver NADPH synthesis and its availability for mono-oxygenase reactions. In this study we further evaluated the mutual relationship between glucose and drug metabolism and the effect of sulphonylurea therapy by using genetically obese female mice. The mice were treated with glibenclamide, phenobarbital or both. Glibenclamide reduced blood glucose and plasma insulin levels indicating improved insulin sensitivity in the mice. Total glucose phosphorylating, delivering and NADPH generating enzyme activities were reduced together with decreased microsomal protein content and the amount of smooth endoplasmic reticulum in the liver. Phenobarbital had an opposite effect: the drug induced liver drug metabolism and increased hepatic glucose phosphorylating and NADPH generating enzyme activities. Treatment with glibenclamide seems to reduce serum immunoreactive insulin levels, microsomal enzyme function and NADPH generating enzyme activities in genetically obese mice.

Animals↗
PubMed1990

Lipid peroxides, glutathione peroxidase, high density lipoprotein subfractions and apolipoproteins in young adults.

Lipid peroxides have been implicated in the initiation of atherogenesis. In this study of 23 young healthy subjects, high levels of serum lipid peroxides were associated with low serum HDL2 cholesterol concentrations and low HDL2/HDL3 cholesterol and apolipoprotein A-I/A-II ratios. Low levels of LDL cholesterol and apolipoprotein B, and low apolipoprotein B/A-I ratios were typical of subjects with high serum glutathione peroxidase activities. Serum lipid peroxide levels varied widely in subjects without abnormal cholesterol, HDL cholesterol or LDL cholesterol concentrations. This variation may play a role in the frequent occurrence of coronary artery disease in normolipidaemic individuals.

Adult↗
PubMed1989

Effect of short-acting nitroglycerin on heart rate: evaluation by a self-monitoring device.

The efficacy of two sublingual nitroglycerin formulations was compared in 10 healthy subjects and 10 patients with ischaemic heart disease. A new microcomputerized device was used to record and analyze heart rate. The rise in heart rate began 1-1.5 min after administration of nitroglycerin tablets and was maximal within 3 min. The effect was more rapid with a quickly dissolving compound. The recording equipment was reliable, simple to use and inexpensive.

Administration, Sublingual↗