Simultaneous Determination of Telmisartan and Pitavastatin Calcium in Intestinal Perfusate by HPLC: Application to Intestinal Absorption Interaction Study

Background: Hypertension and hypercholesterolemia are two main physiological risk factors of cardiovascular disease, and commonly occur in combination. Multicompound combination therapy is rational for the treatment of concurrent hypertension and hypercholesterolemia, while telmisartan and pitavastatin calcium can be used as a potential drug combination. Objective: The aim of this paper is to study the intestinal absorption and absorption interaction of telmisartan and pitavastatin calcium. Methods: An HPLC method was developed and validated to determine telmisartan and pitavastatin calcium in intestinal perfusate simultaneously. The in situ single-pass perfusion in rats was utilized to investigate the effects of concentrations, intestinal segment (duodenum, jejunum, ileum and colon) and co-administrated drugs on absorption. Results: The effective permeability coefficient and the absorption rate constant of telmisartan were higher in the duodenum as compared to other intestinal segments. However, the intestinal absorption of pitavastatin calcium was not segmental dependent. The effective permeability coefficient and absorption rate constant have no significant difference among three concentrations of telmisartan, pitavastatin calcium individually and their combination. Conclusion: The results showed that telmisartan and pitavastatin calcium were transported passively, and telmisartan and pitavastatin calcium could be absorbed well in all intestinal segments. The intestinal absorption parameters revealed the absence of any intestinal absorption interaction when co-administered. Lay Summary: Co-administration of telmisartan and pitavastatin calcium can provide a potential therapeutic strategy for the treatment of concurrent hypertension and hypercholesterolemia. We are investigating the intestinal interaction of these two drugs in rats using the developed HPLC method and in situ single-pass perfusion technology. We will calculate some parameters after administrating two types of drugs either separately or together, which help reflect changes regarding intestinal absorption and penetration. Compared with telmisartan and pitavastatin calcium administrated separately, if parameters significantly change after co-administration, it proves the existence of the intestinal interactions. Moreover, the results might contribute to clinic drug monitoring.

Plant growth and total Nitrogen absorption rate in leachate with water hyacinth (Eichhornia crassipes)

Phytoremediation is a simple technique of wastewater processing by utilizing the plant activity to vanish, replace and stabilize or destroy the pollutant either organic compound or inorganic. This research utilizes Eichhornia crassipes as the biofilter in handling the leachate produced from organic waste degradation. The purposes of this research are to find out the plant growth rate and total Nitrogen (N) absorption in leachate by the Eichhornia crassipes. The experiment shows that the concentration of leachate affects the absorption rate of total N and wet weight of the plant. The model was fit to the experimental data. The metabolism reaction rate constant ( ) and absorption rate constant ( ) at leachate concentration 5%, 10%, 15%, 20%, 25% and 30% were measured. The highest reaction rate constant and absorption rate constant were 5% of leachate concentration where = 0.008042/day and = 2.30811/day, whilst at the leachate concentration of 30% reaction rate constant and absorption rate constant were the lowest where it reached = 0.00029/day and = 0.04576/day. The absorption ability of water hyacinth to absorb the N which contained in the leachate was affected by the metabolism reaction rate of nitrogen in the plant and the reaction rate of nitrogen degradation into ammonia (NH4) and nitric ion (NO3) in the plant root. The leachate concentration affected the efficiency of N absorption by the water hyacinth. The efficiency of N absorption at leachate concentration of 5; 10; 15; 20; 25 and 30 were 89.81%, 68.99%, 49.51%, 36.32%, 30.28% and 21.64% respectively. Overall, this technique presents a simple technique approach and the utilization of elements contained in the leachate as the nutrition for plant.

Absorption Enhancing Effect of Sodium Dodecyl Sulfate on Metformin Hydrochloride in Rat Colon

The aim of this study was to observe the absorption enhancing effect of sodium dodecyl sulfate on metformin hydrochloride in colon of rat. Using in vivo intestinal loop model in rat while the ileum was took as blank group and colon as the experiment groups with different concentration of sodium dodecyl sulfate (1%, 2%, 4%). The colon/ileum ratio of the absorption rate constant of metformin hydrochloride was evaluated through calculating the residual dose of circulating solution in presupposition time points. Intergroup absorption rate constant and the rising percent of the absorption rate constant were different significantly (P<0.05). The absorption rate constant of colon were -0.22±0.03, -0.37±0.06, -0.89±0.09, -0.86±0.05μg•h-1•cm-1 (n=6) and the rising percent of the constant absorption value were 68.66 ± 8.28%, 304.88 ± 28.76%, 293.75 ± 33.19% (n=6), respectively. The result showed that the absorption of metformin hydrochloride was increased with the concentration of sodium dodecyl sulfate. However, the absorption rate constant reached maxium when the concentration of sodium dodecyl sulfate was 2%, this may be because the circulating metformin hydrochloride solution could be more viscous which affect the absorption of metformin hydrochloride when sodium dodecyl sulfate was raised. In conclusion, the absorption of metformin hydrochloride can be promoted by sodium dodecyl sulfate in the colon of rat and this can provide biophamaceutics data for novel pharmaceutical preparation.

Pharmacokinetic-Pharmacodynamic Modeling of Unboosted Atazanavir in a Cohort of Stable HIV-Infected Patients

ABSTRACTLimited data on the pharmacokinetics and pharmacodynamics (PK/PD) of unboosted atazanavir (uATV) in treatment-experienced patients are available. The aim of this work was to study the PK/PD of unboosted atazanavir in a cohort of HIV-infected patients. Data were available for 58 HIV-infected patients (69 uATV-based regimens). Atazanavir concentrations were analyzed by using a population approach, and the relationship between atazanavir PK and clinical outcome was examined using logistic regression. The final PK model was a linear one-compartment model with a mixture absorption model to account for two subgroups of absorbers. The mean (interindividual variability) of population PK parameters were as follows: clearance, 13.4 liters/h (40.7%), volume of distribution, 71.1 liters (29.7%), and fraction of regular absorbers, 0.49. Seven subjects experienced virological failure after switch to uATV. All of them were identified as low absorbers in the PK modeling. The absorption rate constant (0.38 ± 0.20 versus 0.75 ± 0.28 h−1;P= 0.002) and ATV exposure (area under the concentration-time curve from 0 to 24 h [AUC0–24], 10.3 ± 2.1 versus 22.4 ± 11.2 mg · h · liter−1;P= 0.001) were significantly lower in patients with virological failure than in patients without failure. In the logistic regression analysis, both the absorption rate constant and ATV trough concentration significantly influenced the probability of virological failure. A significant relationship between ATV pharmacokinetics and virological response was observed in a cohort of HIV patients who were administered unboosted atazanavir. This study also suggests that twice-daily administration of uATV may optimize drug therapy.

Pharmacokinetics of human chorionic gonadotropin after i.m. administration in goats (Capra hircus)

The present investigation addresses the pharmacokinetics of human chorionic gonadotropin (hCG), intramuscularly (i.m.) administered to goats. Nine pluriparous does of the Boer goat breed, 2–6 years of age and weighing 45–60 kg, were administered 500 IU hCG (2 ml Chorulon) deep into the thigh musculature 18 h after superovulatory FSH treatment. Blood samples were drawn from the jugular vein at 2 h intervals for the first 24 h, at 6 h intervals until 42 h, and at 12 h intervals until 114 h after administration. After centrifugation, plasma hCG concentrations were determined by electrochemiluminescence immunoassay. Pharmacokinetical parameters were as follows: lag time, 0.4 (s.e.m. 0.1) h; absorption rate constant, 0.34 (s.e.m. 0.002) h; absorption half-life, 2.7 (s.e.m. 0.5) h; elimination rate constant, 0.02 (s.e.m. 0.002) h; biological half-life, 39.4 (s.e.m. 5.1) h; and apparent volume of distribution, 16.9 (s.e.m. 4.3) l. The plasma hCG profile was characterized by an absorption phase of 11.6 (s.e.m. 1.8) h and an elimination phase of 70.0 (s.e.m. 9.8) h, with considerable individual variation in bioavailability and pharmacokinetical parameters. Biological half-life was negatively correlated (P<0.05) with peak concentration (r=−0.76), absorption rate constant (r=−0.78), and elimination rate constant (r=−0.87). The results indicate that after rapid absorption, hCG remains in the circulation for an extended period. This has to be taken into account when assessing the stimulatory response to hCG treatment on an ovarian level.