The nonskeletal effects of vitamin D3 and the threshold limit associated with the risk of health complications.

OBJECTIVE: To evaluate the threshold limit of vitamin D3 associated with the risk of nonskeletal health complications in humans. BACKGROUND: Vitamin D3 deficiency is primary caused by a reduced sun exposure, consequent limiting of vitamin D3 production in the skin, and low intake of food with this vitamin. METHODS: Ninety-two adults (25-95 years old) were admitted to III. Internal clinic or examined in outpatient department of The University hospital in Bratislava. Vitamin D3 levels were determined using electrochemical luminescence immunoassay. The least square method for the results processing was used. RESULTS: Vitamin D3 level 16 ng/ml may be threshold limit for the risk of hypertension, ischaemic heart disease, renal insufficiency and diabetes mellitus. A higher occurrence of the observed diseases was in female and male patients with vitamin D3 levels<16 ng/ml.The highest increase of occurrence of diabetes mellitus in women for vitamin D3<16 ng/ml (160%) compared to vitamin D3≥16 ng/ml (40%) was observed. Concerning the men, the highest increase refers to ischaemic heart disease (67%). CONCLUSION: The limit value of vitamin D3, 16 ng/ml, confirmed the association between vitamin D3 insufficiency and the presence of hypertension, ischaemic heart disease, renal insufficiency and diabetes mellitus. Its relation to age, sex and other variables was detected (Tab. 1, Fig. 5, Ref. 27).

Influence of Circulation System on Estimation of Absorption and Elimination Constant after per oral Drug Administration: A Reanalysis.

This study aimed to identify the cause of atypical shape of measured concentration-time profile in the peak area by one compartment open model with a lag time (Bateman function with a lag) after single dose oral administration of drug published in "Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Application" by Gabrielsson and Weiner (1997) and two concentration profiles after frequent sampling oral glucose tolerance test. Following the oral administration of 100 µg of substance A to human volunteer, frequent sampling was carried out and concentration-time profiles were obtained. Our hemodynamic circulatory structural model capable of parameters estimation of circulation and gastrointestinal subsystem to explain the plateau within the interval 40-100 min (substance A) and 15-30 min (glucose) of the measured concentration-time profile was developed. The mean residence time, the rate constants of absorption and elimination parameters of our model were calculated. Comparing to the Bateman function, our results demonstrate better approximation of the substance A and glucose concentration-time profile and estimation of absorption rate constant by our structural model. Obtained model results indicate that the atypical shape of measured concentration-time profile of single dose oral administration of drug was probably caused by the gastrointestinal and circulation system with deep compartment. This applies to the substances with high coefficient of absorption.

Effect of gastric emptying and entero-hepatic circulation on bioequivalence assessment of ranitidine.

The aim of study was to compare the bioavailability of ranitidine obtained from either Ranitidine (300 mg tablet; LPH® S.C. LaborMed Pharma S.A. Romania: the test formulation) and Zantac® (300 mg tablet; GlaxoSmithKline, Austria: the reference formulation). Twelve, Romanian, healthy volunteers were enrolled in the study. An open-label, two-period, crossover, randomized design was used. Plasma levels of ranitidine were determined using the validated, high-pressure liquid chromatography (HPLC) method. The physiologically motivated time-delayed model was used for the data evaluation and a paired Student's t-test and Schuirmann's two one-sided tests were carried out to compare parameters. Nonmodeling parameters (AUC(t), AUC, C(max), T(max)) were tested by the paired Student's t-test and the 90 confidence intervals of the geometric mean ratios were determined by Schuirmann's tests. Paired Student's t-test showed no significant differences between nonmodeling and modeling parameters. The results of the Schuirmann's tests however indicated significant statistical differences with reference to AUC(t), AUC, C(max), T(max) and other modeling parameters, especially MT(c) and τ(c). Schuirmann's tests revealed significant bioequivalence between ranitidine formulations using the modeling parameters MRT and n. The presented model can be useful as an additional tool to assess drug bioequivalence, by screening for disruptive parameters.