M.J. Diez

Therapeutic effects of psyllium in type 2 diabetic patients

Objective: The aim of this study was to evaluate the effects of psyllium in type 2 diabetic patients.Design: The study included three phases: phase 1 (1 week), phase 2 (treatment, 14 g fibre/day, 6 weeks) and phase 3 (4 weeks). At the end of each phase a clinical evaluation was performed after the ingestion of a test breakfast of 1824.2 kJ (436 kcal). Measurements included concentrations of blood glucose, insulin, fructosamine, GHbA1c, C-peptide and 24 h urinary glucose excretion. In addition, uric acid, cholesterol and several mineral and vitamin concentrations were also evaluated.Setting: The study was performed at the Department of Pharmacology, Toxicology and Nursing at the University of León (Spain).Subjects: Twenty type 2 diabetic patients (12 men and 8 women) participated in the study with a mean age of 67.4 y for men and 66 y for women. The mean body mass index of men was 28.2 kg/m2 and that of women 25.9 kg/m2.Results: Glucose absorption decreased significantly in the presence of psyllium (12.2%); this reduction is not associated with an important change in insulin levels (5%). GHbA1c, C-peptide and 24 h urinary glucose excretion decreased (3.8, 14.9 and 22.5%, respectively) during the treatment with fibre (no significant differences) as well as fructosamine (10.9%, significant differences). Psyllium also reduced total and LDL cholesterol (7.7 and 9.2%, respectively, significant differences), and uric acid (10%, significant difference). Minerals and vitamins did not show important changes, except sodium that increased significantly after psyllium administration.Conclusions: The results obtained indicate a beneficial therapeutic effect of psyllium (Plantaben®) in the metabolic control of type 2 diabetics as well as in lowering the risk of coronary heart disease. We also conclude that consumption of this fibre does not adversely affect either mineral or vitamin A and E concentrations. Finally, for a greater effectiveness, psyllium treatment should be individually evaluated.

Effects of ispaghula husk and guar gum on postprandial glucose and insulin concentrations in healthy subjects

Objective: The aim of this study was to evaluate, under the same experimental conditions and in the same subjects, the effects of ispaghula husk and guar gum on postprandial glucose and insulin concentrations in healthy female subjects.Design: An oral glucose load with and without fiber was administered in the morning after an overnight fast. The study of the fiber effect was planned according to a randomized and cross-over design.Setting: The study was performed at the Department of Pharmacology, Toxicology and Nursing at the University of León (Spain).Subjects: Ten healthy female volunteers aged 30–48 y with normal body mass indices participated in this study.Results: A significant decrease in mean serum insulin concentrations was observed from 30 to 90 min in the presence of both fibers. The area under the insulin curve was significantly reduced by 36.1% for ispaghula husk and 39.4% for guar gum. The area under the glucose curve was reduced by 11.1% (significant difference) for ispaghula husk and 2.6% for guar gum (no significant difference).Conclusions: According to the results obtained in this study, the administration of ispaghula husk may be beneficial due to its ability to reduce glucose postprandial concentration and especially insulin requirements. Individualization of the treatment would be advisable due to large individual variations observed in glycemic and insulinemic postprandial responses.European Journal of Clinical Nutrition (2001) 55, 235–243

Determination of levamisole by HPLC in plasma samples in the presence of heparin and pentobarbital

Abstract A method which allows for the isolation of levamisole in plasma samples of rabbit which contained pentobarbital and heparin as well, used as an anaesthetic and an anticoagulant respectively, is described in this paper. The subsequent quantification was carried out using a ion-pair high-performance liquid chromatographic method in a reversed and isocratic phase at room temperature, using a UV detection at 225 nm. In our conditions the retention time for the levamisole was about 2.15 minutes and the average percentage of recuperation was that of 73.62%.

Rapid high-performance liquid chromatographic assay of ethynyloestradiol in rabbit plasma.

A method for the determination of ethynyloestradiol in samples of rabbit plasma containing pentobarbital and heparin, the former used as an anaesthetic and the latter as an anticoagulant, has been developed. Quantification was carried out using a reversed-phase high-performance liquid chromatographic (HPLC) method in isocratic mode at room temperature, with electrochemical detection at an applied potential of +1 V vs. Ag/AgCl. Under these conditions, the retention time for ethynyloestradiol was ca. 2.9 min, the average recovery from plasma was 74.5%, and the limit of detection was 10 pg, corresponding to a plasma concentration of 50 pg/ml using 1 ml of plasma. Natural oestrogens, oestriol, oestradiol and oestrone showed peaks that did not interfere with ethynyloestradiol, and retention times of ca. 0.8, 2.4 and 3.4 min, respectively.

Study of the pharmacokinetic interaction between ethinylestradiol and amoxicillin in rabbits

Several antibiotics have been implicated in oral contraception failure when they are administered at the same time as the oral contraceptive (OC) pill. In the present paper, a study about amoxicillin-ethinylestradiol (EE2) pharmacokinetic potential interaction was studied. Two rabbit groups were utilized, the first group received amoxicillin (10 mg/kg) and EE2 (30, 50 and 100 micrograms/kg, respectively), both by intravenous (i.v.) route. The second group received amoxicillin (oral route, 10 mg/kg/day) and EE2 (i.v. route, 100 mu/kg) on day 1, 4 and 8 of antibiotic treatment, respectively. After compartmental (two-compartment open model) and non-compartmental analysis of plasma concentrations, the statistical study (ANOVA p < or = 0.05) revealed that the presence of amoxicillin did not modify the EE2 distribution and elimination pharmacokinetic parameters (by comparison with those obtained in a previous study where EE2 was administered alone). There also were no significant differences with the time of amoxicillin oral treatment.

Bioavailability of levamisole after intramuscular and oral administration in sheep.

AIMS To determine the bioavailability of levamisole in sheep. METHODS Levamisole was administered to three groups of six Merino sheep orally and intramuscularly at three dose levels of 5, 7.5 and 10 mg/kg. There was a washout period of 1 week between treatments. Blood samples were collected by jugular venepuncture and plasma was separated immediately by centrifugation and stored at 20 degrees C until analysed. The levamisole concentration in plasma was determined by high performance liquid chromatography with a U.V. detection method. Individual plasma levamisole concentration-time data were analysed using the compartmental method. RESULTS The values obtained for k(a), C(max), t(max) and F show a moderate rate and extent of absorption after oral administration of levamisole while, after intramuscular administration, these values demonstrate a high rate and extent of absorption of levamisole. The intramuscular bioavailability was higher than the oral bioavailability (rate of absorption three-fold faster, extent of absorption 25-33% higher and C(max) two-fold higher). The Friedman test involving dose and route of administration showed that the route of administration affects k(a), C(max), t(max) and F; significant differences were found in these parameters. CLINICAL RELEVANCE On the basis of these data, the recommended routes for the administration of levamisole in sheep are oral for gastro-intestinal nematodiasis and intramuscular for extragastric nematodiasis.

Effects of dietary factors on levodopa pharmacokinetics.

Importance of the field: Levodopa is the most effective treatment for Parkinsons disease, so it is important to understand the pharmacokinetic and pharmacodynamic features of this drug. Considering the pharmacokinetics of levodopa and the factors that can modify it are essential for the clinician when prescribing levodopa products in order to maximize their therapeutic effects. Areas covered in this review: This paper reviews the studies carried out evaluating the interaction between levodopa and dietary factors. What the reader will gain: The reader will gain a greater understanding of the different dietary factors that can affect levodopa pharmacokinetics and, thus, the therapeutic response that is obtained with this drug in several situations. Take home message: An understanding of the pharmacokinetics of any drug is crucial for the establishment of its optimal therapeutic regimen, but this assumes a special importance with levodopa, due to its extensive presystemic metabolism, rapid absorption in the proximal small intestine and short plasma half-life. Major problems with levodopa treatment are the fluctuations in clinical response experienced in patients with advanced Parkinsons disease that sometimes are related to the peripheral pharmacokinetics of levodopa. Studies of levodopa interactions are very important to improve patient response to this drug.

Pharmacokinetics of levamisole in sheep after intravenous administration

The pharmacokinetics of levamisole at doses of 5, 7.5 and 10 mg/kg were determined after its intravenous administration to eighteen healthy Merino sheep. Using compartmental analysis, the disposition of the drug best fitted a two-compartmental open model. The mean values for the compartmental volume of distribution at steady state (Vss) were 2.034 +/- 0.23 I, 2.347 +/- 0.720 and 2.001 +/- 0.367 I/kg for each dose, respectively, and values obtained using the statistical moment theory were 2.141 +/- 0.269,2.390 +/- 0.536 and 2.140 +/- 0.345 l/kg for each dose, respectively. There were no dose-related differences (one-way ANOVA) in the constants describing distribution and elimination phases (alpha and beta) or Vss, but significant differences were detected in the total body clearance (Cl) and the area under the plasma concentration-time curve (AUC). After non-compartmental analysis, no significant differences were found when the parameters lambda (the linear terminal slope) and Vss were compared, but significant differences were detected in Cl and AUC. There were no significant differences between the values obtained using the compartmental and non-compartmental analysis when lambda -beta, Cl, Vss, and AUC were compared.

Evolution of the bioavailability and other pharmacokinetic parameters of levodopa (with carbidopa) in rabbits

Levodopa pharmacokinetics show important inter- and intraindividual differences when it is administered by the oral route. As a result of fluctuating drug plasma concentrations, patients may develop motor fluctuations and dyskinesias. Therefore, it is important to perform studies on levodopa pharmacokinetics in the same individual. The aim of this study was to contribute to a better knowledge of the evolution of the pharmacokinetics of levodopa administered with carbidopa. The study involved the oral administration of 20/5 mg/kg levodopa/carbidopa to rabbits for two different time periods (7 or 14 days), due to the fact that inhibition of aromatic L-amino-acid decarboxylase by carbidopa is not immediate. After 7 days of treatment, the levodopa AUC increased by 12.6% from day 1 (range: 114.2-150.7 microg.min/ml) to day 7 (range: 131.1-166.0 microg.min/ml) and C(max) increased by 9.6% (range: 1.90-2.86 microg/ml on day 1 and 2.12-3.13 microg/ml on day 7). After 14 days of treatment, the increase in AUC was 17.0% (range: 119.6-160.1 microg.min/ml on day 1 and 142.9-172.7 microg.min/ml on day 14) and C(max) increased by 6.5% (range: 2.29-2.96 microg/ml on day 1 and 2.41-3.07 microg/ml on day 14). The values obtained for C(min) (sample obtained immediately before levodopa/carbidopa administration) in both groups increased progressively with the duration of the treatment. C(max) and AUC values were very similar after 7 or 14 days of treatment. The time needed for C(min) stabilization was slightly higher, because we found significant differences until day 11 of treatment.

Pharmacokinetics of ethinyloestradiolin rabbits after intravenous administration

Abstract The pharmacokinetics of ethinyloestradiol (EE 2 ) after intravenous administration of 30, 50 and 100 μg.kg −1 was investigated in rabbits. A high-performance liquid chromatographic (HPLC) method with electrochemical (EC) detection was used to measure EE 2 in plasma samples in order to avoid the interferences of natural oestrogens. After compartmental analysis, the disposition of EE 2 was well described by a two-compartmental open model with mean values of: α = 0.3448 ± 0.2922, 0.1965 ± 0.1755, 0.3058 ± 0.1225 min −1 , and β = 0.0137 ± 0.0018, 0.0140 ± 0.0065, 0.0198 ± 0.0066 min −1 , for the three doses studied, respectively. There were no dose-related differences (ANOVA, P ss , but significant differences were detected in clearance (90.9 ± 18.7; 80.6 ± 17.6; 116.3 ± 21.5 ml.min −1 .kg −1 ) between the 100 μg.kg −1 group and lower dose groups. The AUC increased significantly with the doses (341.7 ± 67.1; 645.8 ± 143.9; 892.2 ± 211.9 ng.min.ml −1 ). After non-compartmental analysis there were no significant differences in λ, MRT or V ss as a function of dose, but these differences were significant when Cl or AUC were compared. There were no significant differences in AUC or Cl values obtained by compartmental and non -compartmental analysis.