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Biomedical subjects

V Hutt

Publications and source records attributed to V Hutt.

At least 19 recordsLinked to original sources
PubMed1992

Evaluation of bioavailability and pharmacokinetics of two isosorbide-5-mononitrate preparations in healthy volunteers.

The objective of this study was to determine both the pharmacokinetic parameters and the bioavailability of two commercial 20-mg isosorbide-5-mononitrate (IS-5-MN) preparations (test and reference preparation) after single oral administration. For this purpose, the test and the reference preparation were examined in 24 healthy male volunteers according to a randomized 2-way cross-over design, blood samples were withdrawn up to 24 hours postadministration, and plasma concentrations of IS-5-MN were quantified by a gas chromatography (GC) method. Both preparations led to peak plasma levels of approximately 360 ng/mL IS-5-MN in the mean 0.76 hour (test) and 0.94 hour (reference preparation) after application; the plasma half-lives were about 5.2 hours, and for the areas under the curve (AUC(0-infinity)), mean values of 2741 (test preparation) and 2742 hour.ng/mL (reference preparation) were found. The statistical comparison (analysis of variance, confidence intervals) of the pharmacokinetic parameters found in the study resulted in bioequivalence of both IS-5-MN preparations. The undesired side effects/concomitant symptoms observed are known to occur after IS-5-MN administration.

Administration, Oral↗
PubMed1991

[Plasma and urine kinetics of amitriptyline oxide and its metabolites. Comparison of intravenous infusion and oral administration in volunteers].

The study objective was to obtain detailed information on the plasma and urine kinetics of amitriptylinoxide (CAS 4317-14-0) and its metabolites. For this reason, 60 mg of amitriptylinoxide was administered to 12 subjects, both by intravenous infusion and by oral dosage, in a study performed according to a randomized two-way cross-over design. In plasma, we succeeded in analyzing the metabolites amitriptyline and nortriptyline in addition to the parent substance amitriptyloxide. The tests for the parent substance amitriptylinoxide revealed maximum plasma levels of 721 and 686 ng/ml at 1.96 h (i.v. infusion) and 0.82 h (oral formulation), respectively. Mean values of 2331 (infusion) and 1714 h.ng/ml (oral formulation) were determined for the area under the curve from time 0 to infinity AUC (0-infinity). We also produced a comprehensive evaluation of amitriptyline, however, this was not possible for the metabolite nortriptyline. In urine, we succeeded in a reliable quantification of 4 metabolites, namely cis-OH-amitriptylinoxide, trans-OH-amitriptylinoxide, amitriptyline and OH-nortriptyline, in addition to the parent substance amitriptylinoxide. In individual samples, nortriptyline, cis-OH-amitriptyline and trans-OH-amitriptyline were additionally identified. In the course of the study, there were no reports or observations of any adverse reactions in addition to the side effects known for amitriptylinoxide from literature. There were no clinically relevant differences in tolerability observed between these two preparations.

Administration, Oral↗
PubMed1989

Urinary recovery and tolerability of FCE 22101 following single intravenous administration under restricted and high fluid intake.

The urinary recovery and tolerability of FCE 22101, a broad spectrum injectable penem, were investigated in a multicentre single-blind randomized crossover study of 60 healthy male volunteers. Single 1 g doses of FCE 22101 or placebo were given by intravenous bolus at weekly intervals. FCE 22101 was given either after intake of 750 ml water (treatment A) or after 8 h of water restriction (treatment B). Placebo was given under water restriction (treatment C). Urine samples obtained at timed intervals were assayed for FCE 22101 and its metabolites P1 and P2 by HPLC. The 24 h urinary recoveries of the parent drug and its metabolites were similar after treatments A and B. Mean recoveries +/- S.D were 29 +/- 13% (FCE 22101), 31 +/- 12% (P1) and 7 +/- 2% (P2) of the dose. Transient suprapubic pain or dysuria, or both, were reported by two subjects after treatment A and by six subjects after treatment B. Symptoms were associated with low urine volumes at 0-2 h and low urinary recovery of FCE 22101 and metabolite P1.

Adult↗
PubMed1989

[Bioavailability and pharmacokinetics of a new nifedipine preparation in healthy volunteers].

In the course of this trial the bioavailability and the essential pharmacokinetic parameters of a newly developed 10 mg nifedipine preparation were to be determined in comparison to a marketed reference preparation after single oral administration. For this purpose, the test and the reference preparation were examined in 16 healthy volunteers according to a randomized 2-way cross-over design (latin square), blood samples were withdrawn up to 16 h p.a. and plasma concentrations of nifedipine and NPO (primary metabolite of nifedipine) were quantified by a HPLC method. Both preparations led to mean maximum concentrations of nifedipine in plasma of 110 mg/ml about 0.5 h p.a.; the mean termial half-lives were 1.8 h (test preparation) and 1.7 h (reference preparation). The data found for the metabolite NPO largely corresponded to those of the parent substance, thus equal metabolisation and adequate pharmaceutical quality of the two galenics may be presumed. Statistical comparison (ANOVA, Pratt-Wilcoxon test) did not reveal any significant differences between the test and reference preparation and, apart from a minor deviation, confidence intervals according to Westlake were sufficiently small, such that the two formulations may be considered bioequivalent. No differences of clinical relevance were detected between the two preparations in assay. The undesired side effects/concomitant symptoms known after nifedipine administration were observed.

Adult↗
PubMed1988

[Studies of the pharmacokinetics and bioavailability of a new trimethoprim/sulfamethoxazole preparation in healthy volunteers].

The objective of this study was to determine both the pharmacokinetic parameters and the bioavailability of a newly developed trimethoprim/sulfamethoxazole preparation (cotrimoxazole, Kepinol forte, 160 mg of trimethoprim/800 mg of sulfamethoxazole) in comparison with a reference preparation customary in trade and registered according to the AMG 1976, after single oral administration. For this purpose the test and the reference preparation were examined in a randomized 2-way crossover design (Latin square) in 12 volunteers each. Both dosage forms led to maximum plasma levels of approx. 1250 ng/ml of trimethoprim and about 40 micrograms/ml of sulfamethoxazole 1.5-2 h after application; the plasma half-lives were about 9 h for trimethoprim and around 8.5 h for sulfamethoxazole. The statistical comparison (ANOVA, confidence intervals according to Westlake, Pratt-Wilcoxon test) of the pharmacokinetic parameters found in the study resulted in bioequivalence of the newly developed trimethoprim/sulfamethoxazole preparation and the reference preparation. Furthermore, after the administration of both preparations no marked side effects worth mentioning were observed, suggesting a good and comparable clinical tolerability of the two preparations.

Adult↗
PubMed1987

[Lithogenicity and bile acid pattern in choleretic administration (3-n-butoxy-1-phenoxy-propanol: febuprol) in patients with functional right upper quadrant pain].

10 patients with right upper quadrant pain were treated with a choleretic agent (Febuprol; 3 X 200 mg t. i. d.) and placebo in a cross-over double dummy technique for 16 weeks. Lithogenic index, bile acid profile and serum lipids were determined every 4 weeks. During Febuprol application the clinical symptoms were relieved (0.87 +/- 1.3 vs. 1.39 +/- 0.21 (placebo); p less than 0.05, semiquantitative score). Biliary lithogenicity (1.45 +/- 0.6 vs. 1.09 +/- 0.12; n. s.), bile acid profile and serum lipids showed no statistically significant change, although serum cholesterol levels seemed to fall during Febuprol application.

1-Propanol↗
PubMed1984

[Wheat bran-type roughage reduces the lithogenicity of bile].

The effect of 30 g wheat bran on the lithogenic potency of bile was studied in ten healthy males (age 25.5 +/- 0.76 years; height 182.9 +/- 2.1 cm, weight 76.8 +/- 2.3 kg). Wheat bran was taken for over six weeks, at 15 g twice daily. Bile fluid was sucked out from the prepapilla after bile stimulation. Contraction of the gallbladder was checked by ultrasound. Concentration of total bile acids and bile acid spectrum, as well as the concentration of phospholipids, remained unchanged for the six weeks of increased wheat bran intake. Cholesterol concentration in bile decreased from 3.27 +/- 0.89 mmol/l to 2.50 +/- 0.67 mmol/l. The lithogenic index fell from 1.01 +/- 0.14 to 0.67 +/- 0.11. Concentrations and composition of lipids and lipoproteins in serum remained unchanged. An increased intake of wheat bran was thus shown to be a decisive dietary measure in the prevention and treatment of cholesterol gallstones.

Adult↗
PubMed1984

[Composition of VLDL, LDL and HDL lipoprotein fractions in type IIa, IIb, III, IV, and V hyperlipemia patients in comparison with healthy individuals].

The chemical composition of VLDL, LDL and HDL was studied in 82 patients with primary hyperlipoproteinaemia (37 type IIa, 7 type IIb, 3 type II, 25 type IV, 10 type V) and in ten metabolically normal individuals. Lipoprotein fractions were prepared by preparative ultracentrifugation. Each fraction was analysed for cholesterol, triglycerides, phospholipids and protein. Differences between patients and normal individuals, and between the individual types of hyperlipoproteinaemia were evident in the composition of all three lipoprotein fractions.

Aging↗
PubMed1983

[Effect of a clofibrate-inositol nicotinate combination on lipids and lipoproteins in primary hyperlipoproteinemia of types IIa, IV and V].

The effect of a combination of clofibrate and inositol nicotinate (Liporeduct forte, Liporeduct) on lipids and lipoproteins in 20 patients with primary hyperlipoproteinemia (10 type IIa, 7 type IV and 3 tyV) was investigated over a period of 16 weeks. The daily doses of clofibrate and inositol nicotinate was 1,5 g and 2,4 g in the type IIa and 1,5 g and 900 mg in the types IV and V. Placebo was given before and after the treatment period. In the type IIa total cholesterol decreased from 345 +/- 35 to 285 +/- 31 mg/dl; the triglycerides were lowered from 121 +/- 12 to 94 +/- 7 mg/dl. These changes were mainly due to a decrease in low density lipoprotein (LDL)-cholesterol by 18% and a reduction in very low density lipoprotein (VLDL)-triglycerides of 42%. In the types IV and V a triglyceride reduction of 30% and 76% could be observed. In both types, these changes were mainly caused by a decrease in VLDL-triglycerides (type IV: -34%; type V -77%). Total cholesterol was influenced insignificant in these two types. High density lipoprotein (HDL)-cholesterol fell in the types IIa and IV; in the type IV an increase of 24% could be observed. Phospholipids and proteins behaved in an analogous fashion. The percentual composition of the lipoprotein fractions VLDL, LDL and HDL didn't change under treatment in the types IIa and IV. In the type V, a shift in the direction of type IV could be observed. The combination of clofibrate and inositol nicotinate was well tolerated.

Clofibrate↗
PubMed1983

Changes in the concentration and composition of lipids and lipoproteins in primary hyperlipoproteinemia during treatment with bezafibrate.

The effect of 2-(4-chlorobenzoyl-aminoethyl-phenoxy)-2-methylpropionic acid (bezafibrate, Cedur) at doses of 3 x 150 mg and 4 x 150 mg daily on lipids and lipoproteins in 27 patients (3 type IIa, 7 type IIb, 1 type III, 12 type IV and 4 type V) was investigated over a period of 24 weeks in a single-blind study. The lower dose was administered for the first 12 weeks and then the higher dose was given. Plasma triglycerides were reduced in all types. This was mainly caused by a massive reduction in VLDL triglycerides. Plasma cholesterol decreased in the types IIa, IIb, III as a result of the reduction of the LDL cholesterol. In type IV, the plasma cholesterol concentration remained unchanged because of a significant rise in the LDL cholesterol (+14%). The HDL cholesterol rose in all types, statistically significantly in the type IV. Phospholipids and protein behaved in an analogous fashion. In comparison with a control group, the lipoprotein fractions VLDL, LDL and HDL retained their abnormal composition in the types IIa, IIb and IV even when the lipid concentrations were massively lowered by bezafibrate. The drug treatment only led to a reduction of circulating lipoproteins in the blood, but didn't contribute to a normalisation of the lipoprotein composition. In the type V, a shift in the direction of type IV was observed. Bezafibrate proved to be well tolerated.

Aged↗
PubMed1983

[Effect of beta-pyridylcarbinol on lipids and lipoprotein in primary type IIa hyperlipoproteinemia].

The effect of long-term treatment over 16 weeks with beta-pyridylcarbinol (test substance Ronicol 300) on lipids and lipoproteins was investigated in 10 patients with primary hyperlipoproteinemia type IIa. A placebo period preceded and followed the treatment period. The lipoprotein fractions VLDL, DL and HDL (very low density lipoproteins, low density lipoproteins and high density lipoproteins, respectively) were isolated by preparative ultracentrifugation. beta-Pyridylcarbinol reduced total cholesterol from 410 +/- 39 mg/dl to 319 +/- 19 mg/dl (p less than 0.05). The decrease was mainly caused by a reduction in LDL-cholesterol by 25%. The HDL-cholesterol rose only slightly during treatment. The reduction in total triglycerides (132 +/- 12 mg/dl to 110 +/- 12 mg/dl) was less marked. The decrease was attributable to a reduction in VLDL- and LDL-triglycerides. Phospholipids and proteins behaved in an analogous fashion. The composition (in %) of the lipoprotein fractions VLDL, LDL and HDL didn't change under treatment. The typical nicotinic acid flush could be observed in all 10 patients.

Female↗
PubMed1982

[Bezafibrate in primary hyperlipidemias (author's transl)].

The effect of long-term treatment over 40 weeks with Bezafibrate on lipids and lipoproteins was investigated in 27 patients with primary hyperlipoproteinemias (hlp) (12 patients with hlp type IV, 7 patients with type IIb, 3 patients with type IIa, 4 patients with type V and 1 patient with type III). Bezafibrate reduced total cholesterol by 16%, whereas HDL-cholesterol increased by 28% and 36% (p less than 0.05). Serumtriglycerides decreased by 59% (450 mg Bezafibrate daily) and by 66% (600 mg Bezafibrate daily) statistically significant (p less than 0.05). In hyperlipidemias type IV, IIb, IIa and V increases of HDL-cholesterol could be observed. The course of LDL-cholesterol was different in the various types of hlp. The postheparin-lipoprotein-lipase (PHLA) was activated by treatment with Bezafibrate from 10.5 +/- 0.7 to 14.7 +/- 0.7 and 15.5 +/- 0.8 mumol FFA/ml/h or by 30% (p less than 0.05). Only few side-effects during treatment with Bezafibrate could be ascertained.

Bezafibrate↗
PubMed1980

[Effect of etofylline clofibrate on the composition of lipoproteins in hyperlipidaemia type IIb and IV (author's transl)].

Efficacy of 1-(theophyllin-7-yl)-ethyl-2[2-(p-chlorophenoxy)-2-methylpropionate] (etofylline clofibrate, Duolip) (3 x 250 mg) was evaluated in a double-blind cross-over study in 20 patients of type 11b (10 and type IV (10) in comparison to a commercial drug combination (= standard preparation) of clofibrate (3 x 500 mg) and beta-pyridylcarbinol hydrogentartrate (3 x 25 mg). This standard preparation was known from clinical results to be superior over clofibrate in antilipaemic potency. All patients had been already on a diet for several months and in majority were additionally treated with antihyperlipaemic drugs. The treatment periods lasted over 8 weeks each. They were introduced by placebo phases of 4 weeks duration. Between the treatment periods with etofylline clofibrate and with the standard preparation, placebo phases of 4 weeks were inserted, too. The results indicate, that between etofylline clofibrate and the standard preparation there are no remarkable differences and thus 750 mg etofylline clofibrate correspond to 1500 mg clofibrate combined with 75 mg beta-pyridylcarbinol hydrogentartrate in their efficiencies. Since the clofibric acid proportion of etofylline clofibrate clinically is known as ineffective we postulate a potentiation of its effect by its metabolits to cause this surprising effect. In type IIb the cholesterol was distinctly decreased in the VLDL-fraction by 22% and significantly increased in the HDL-fraction by 22%. In type IV triglycerides and cholesterol dropped in the VLDL by 11% and 16%, resp., unless the LDL-fraction revealed an increase of the lipid content. The lipids of the HDL-fraction did not show any essential alternations. Side effects were not observed. The investigations prove that etofylline clofibrate is suitable for the treatment of hyperlipoproteinaemia with elevated triglycerides and cholesterol.

Adult↗
PubMed1980

Lipids and lipoproteins in hyperlipidemia type IIa during treatment with different lipid lowering drugs.

In the present study we examined the effect of different lipid lowering drugs on lipids and lipoproteins in hyperlipoproteinemia type IIa. We have treated over 24 weeks 10 patients with 900 mg beta-pyridylcarbinol daily, 11 patients with 3 g of xantinolnicotinate, 4 patients with 600 mg bezafibrate daily and 10 patients with a combination of 2.4 g inositolnicotinate and 1.5 g clofibrate daily. One patient with familial hypercholesterolemia (untreated total cholesterol 800 mg%) received a combined drug treatment during 5 years. Total cholesterol decreased to 200 mg%, mainly due to decreases in LDL-cholesterol. However in HDL significant decreases of about 50% could be observed. Treatment with the four different drugs showed significant decrements in low density lipoproteins (LDL) whereas an increase of protective high density lipoproteins could not be observed.

Adolescent↗