Latin American Journal of Pharmacy

Regulation of subcellular location and activity of Cdc2-cyclinb1 is involved in bendamustine-induced G2 arrest

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 Bendamustine is a multifunctional alkylating agent for the treatment of multiple myeloma, with the G2/M arrest-induction ability in human multiple myeloma RPMI-8226 cells, but the mechanism remains ambiguous. In this study, we found bendamustine caused the G2 arrest in 24 h, regulated the phosphorylation status of Cdc2, and blocked the nuclear import of Cdc2-CyclinB1 complex. Pretreatment with ATM/ATR inhibitor caffeine or p38 MAPK inhibitor SB203580 suppressed the phosphorylation of Cdc2 at Thr14/Tyr15 or attenuate the blockade of nuclear import, respectively; however, neither of these two inhibitors nor the combination imposed significant effects on Bendamustine-triggered G2 arrest. Bendamustine-induced blockade of the nuclear translocation dissipated after 48 h, after which, the G2 arrest was maintained through the inhibitory phosphorylation of Cdc2. Taken together, our research suggested that two or more pathways and mechanisms which regulated the cell cycle in a time-dependent manner were involved in the G2 arrest invoked by bendamustine.

Development and biodistribution of trans-resveratrol loaded chitosan nanoparticles with free amino groups

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 The conventional method for preparing chitosan nanoparticles (CS-NPs) leads to the surface amino groups protonated and unable to link other useful moieties. In this study, we optimized the method of sodium chloride precipitation our lab established before to produce CS-NPs with surface free amino groups. The effects of preparation conditions on the size and encapsulation efficiency were examined. As surface amino groups may exert special effect on the NPs biodistribution, in vivo distribution was investigated after intravenous administration to the mice. The optimized CS-NPs were round with the mean diameter of 257 ± 21 nm. Compared with trans-resveratrol solution, the CS-NPs had longer circulation time in vivo. The AUC of CS-NPs in liver was 2.29 fold AUC of the solution. This study demonstrates that not only can the unique CS-NPs be modified to obtain active targeting systems, they are also an excellent candidate for liver targeting treatment.

Effects of adrenalin on ovarian injury formed by ischemia reperfusion in rats

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 In this study, the impacts of adrenalin on ovarian injury caused by ischemia reperfusion were investigated in rats. In addition, it’s been investigated whether there is a correlation between adrenergic receptors and oxidant/anti-oxidant and COX1/COX-2 levels. It’s been observed that the COX-2 level that is responsible for MDA and inflammatory reaction (which are the indicators of oxidative stress in ovarian tissue to which ischemia reperfusion was applied) increased and the COX-1 levels that are responsible for GSH (an endogenic anti-oxidant with protective impact) were depressed. Adrenalin has prevented an increase in MDA and COX-2 activity in the ovarian tissue, to which I/R was applied, and prevented a reduction in GSH and COX-1 activity. However, adrenalin failed to prevent an MDA increase in ovarian tissue, to which alpha-2 adrenergic receptor blocker yohimbine was given (I/R formed), and also failed to prevent a GSH and COX-1 decrease. Adrenalin also failed to inhibit the COX-2 activity increase in ovarian tissue, to which beta blocker was applied. As a result, stimulation of the alpha-2 adrenergic receptors in an ovarian tissue causes an anti-oxidant and protective effect, while stimulation of beta-2 adrenergic receptors causes an anti-inflammatory effect. It’s been thought that adrenalin protects the ovarian tissue against ischemia reperfusion by stimulating the alpha-2 and beta-2 adrenergic receptors.

Protective effects of luteolin on restraint stress-induced liver damage in mice

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 The present study was designed to investigate the protective effects of luteolin, a flavonoid, against acute immobilization-induced liver damage in mice. Mice were immobilized for a period of 6 h daily for three consecutive weeks. Luteolin (25 or 100 mg/kg, i.g.) was administered 30 min before subjecting the animals to restraint stress (RS). Our experiment showed that RS could induce liver damage, with an increase in glutamic-pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) in the liver tissue. Furthermore, the changes of anti-oxidative capacity in liver tissue were also measured. The changes of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase activities (CAT) of stress group were significantly different from those in the control group. However, these changes in stress low and high-doses of luteolin modulation group were improved. These results demonstrated that luteolin has a protective effect against RS-induced liver damage through scavenging both free radicals activity and lipid peroxidation inhibitory effect.

Anti-inflammatory, analgesic activities, and composition of ZCSSWE, an ethanol extract derived from the anti-arthritic chinese herbal formula zha chong shi san wei pill

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 The classical Chinese herbal formula Zha Chong Shi San Wei pill (ZCSSW) has been commonly used in traditional Chinese herbal medicine for hundreds of years to alleviate pain and inflammation. The anti-inflammatory effects of the ethanol extract were examined by using albumin egg-induce paw edema in mice assay and xylene-induced ear edema in mice method. Analgesic activity was evaluated by three models of acetic acid-induced writhing, formalin test and hot-plate test in mice. In addition, the total flavonoids (TF), total polysaccharide (TP) and total alkaloids (TA) in ZCSSWE were determined. The result suggested that ZCSSWE possesses excellent anti-inflammatory activity as well as peripheral and central analgesic properties, TF and TA may be the active ingredients. It also showed that ZCSSWE would be a valuable candidate for further investigation as a new anti-arthritic drug.

Nfluence of mangiferin on membrane bound phosphatases and lysosomal hydrolases in streptozotocin induced diabetic rats

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 The activities of membrane-bound ATPases and lysosomal hydrolases are altered in tissues of streptozotocin (STZ)-induced diabetic rats. Diabetes is stimulating the deterioration of membrane function and weakens the intracellular metabolism. The objective of the present study was to determine the effect of mangiferin, isolated from Salacia chinensis on membrane bound phosphatases and lysosomal hydrolases in the liver and kidney of STZ-induced diabetic rats. In our investigation, the levels of blood glucose and glycosylated haemoglobin were significantly increased in the diabetic rats. Moreover, membrane bound phosphatases and lysosomal hydrolases activities were ominously altered in the liver and kidney of STZ-induced diabetic rats. The treatment of mangiferin (40 mg/kg body weight up to 30 days) significantly brought back the activities of enzymes to near normal, when compared to the experimentally induced diabetic rats. Based on this findings, mangiferin have a substantial outcome on membrane bound phosphatases and lysosomal hydrolases in diabetic condition.

Preparation and evaluation of transdermal drug delivery of ondansetron hydrochloride: effect of vegetable oils as permeation enhancer

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 The objectives of this study were to develop and characterize the matrix type transdermal drug delivery system (TDDS) of ondansetron hydrochloride (ODH). The matrix patch contains different ratios of Eudragit RS 100 and polyvinyl pyrrolidone (PVP) with different concentrations of plasticizer like triethyl citrate (TEC) and dibutyl sebacate (DBS) as well as vegetable oils such as linseed oil, castor oil and eugenol were added and prepared by solvent casting method. Thickness, tensile strength, drug content, moisture content and water absorption studies of the matrix patches were measured. The in vitro drug release and permeation studies were carried out in Franz diffusion cell. The percentage of drug release increased with increasing amounts of PVP and plasticizer, whereas DBS containing patches exhibited higher than TEC containing patches. It may conclude that transdermal patches which use Eudragit RS 100 as the base polymer with higher amount of PVP and plasticizer DBS and additions of linseed oil were suitable for the development of ODH transdermal patches.

Determination of tolbutamide and hydroxytolbutamide by LC–MS/MS in rat and its application to assessment of CYP2C9 activity

2013-01-05T02:01:48Z

Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 A sensitive and selective liquid chromatography–tandem mass spectrometry method (LC–MS/MS) for the determination of tolbutamide (TB) and its metabolite hydroxytolbutamide (HTB) in rat plasma was developed using carbamazepine as an internal standard. Chromatographic separation was performed by an Agilent Zorbax SB-C18 column (150 mmx2.1 mm, 3.5 μm), using the gradient elution of 0.1 % formic acid in water and acetonitrile. Calibration plots were linear over range of 5–1000 ng/mL for TB and 10–2000 ng/mL for HTB in rat plasma. The intra- and inter-day relative standard deviations of the assay were less than 10 % for both TB and HTB. The validated method is successfully used to analyze the influence of bupropion on cytochrome P450-mediated metabolism of TB. The biotransformation rates of TB administered either separately or both simultaneously were compared in this study. The results revealed that bupropion had no significant effect on TB hydroxylation.

Relationship between lactone ratios of 9-nitrocamptothecin and their lactone/carboxylate equilibria in vitro and in vivo

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 The aim of this study was to evaluate the effect of lactone ratios on the lactone/carboxylate equilibria of 9-nitrocamptothecin (9-NC) in vitro and in vivo. The interconversion of lactone and carboxylate forms of 9-NC was studied. Then the lactone ratio vs time profiles of these 9-NC solutions were further investigated in pH 7.4 PBS, rat plasma and blood. 9-NC solutions with different lactone ratios (lactone ratios=100 %, 75 %, 50 %, 25 % and 0 %, respectively) were obtained by modifying the pH of solution and it was found that the effects on lactone/carboxylate equilibrium were in the order: blood cells > plasma albumin > pH. After i.v. administration, between the groups of 100 % and 75 % lactone ratios, the AUC0-t values of lactone 9-NC were almost equal. Therefore, there might be no difference between the anticancer activities of 9-NC solution in the range of 75~100 % lactone ratios.

Involvement of serotonergic system in the antidepressant-like effect of hyperoside from apocynum venetum leaves

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 The present study investigated the antidepressant-like effect of hyperoside extracted from Apocynum venetum leaves in mice using the tail suspension test (TST) and forced swimming test (FST). Hyperoside administration at 10, 20 and 30 mg/kg (p.o.) for 10 days reduced immobility time in both tests. This effect is dose-dependent without influencing the animals’ locomotor activity. Additionally, the monoaminergic mechanisms involved in the antidepressant-like effect of hyperoside in the mouse forced swimming test (FST) were evaluated. The results showed that hyperoside produced an antidepressant-like effect in the FST (10-30 mg/kg, i.g.) and in the TST (10–30 mg/kg, i.g.), without accompanying changes in ambulation distance when assessed in the open-ﬁeld test. The antidepressant-like effect of hyperoside (20 mg/kg, i.g.) was prevented by the pretreatment of mice with ketanserin (5 mg/kg, s.c., a serotonin 5-HT2A receptor antagonist), cyproheptadine (3 mg/kg, i.g., a serotonin 5-HT2 receptor antagonist). On the other hand, the pretreatment of mice with WAY 100635 (0.1 mg/kg, s.c., a serotonin 5-HT1A receptor antagonist) did not block the antidepressant-like effect of hyperoside in the TST. It may be concluded that the hyperoside produces an antidepressant-like effect in the FST and in the TST that is dependent on its interaction with the serotonergic (5-HT2A and 5-HT2 receptors) systems. Taken together, our results suggested that hyperoside deserves further investigation as a putative alternative therapeutic tool that could help the conventional pharmacotherapy of depression.

Marine sponges of the genus neopetrosia with anti-inflammatory activity

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 The present study aimed to investigate the anti-inflammatory effect of marine sponges of the genus Neopetrosia which are abundant in the Colombian Caribbean. We obtained three fractions from a total methanolic extract of Neopetrosia rosariensis and proxima. In vivo activity was measured using λ-carrageenan-induced paw edema assay. The in vitro inhibitory effects were evaluated on myeloperoxidase activity (MPO) and nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor alpha (TNF- α) production. Total extracts of N. rosariensis and N. proxima (100 mg/Kg) significantly inhibited the paw edema of rats (71.74% and 60.06%, respectively). Dichloromethane and methanol fractions of Neopetrosia sponges reduced MPO activity. Only, dichloromethane fraction of N. rosariensis significantly inhibited NO (66%), PGE2 (30.5%) and TNF-α production (72%). Our results show anti-inflammatory activity in extracts and fractions from species of marine sponges belonging to Neopetrosia genus and open the way for complementary studies to purify and identify active molecules.

Perioperative chronic medication management

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 The majority of patients submitted to surgical procedures are on chronic medication. Unfortunately, there are few outcome data about the majority of medications taken in the perioperative period and how clinicians manage chronic medication in this setting. All adult patients consecutively admitted for elective surgery at “Cova da Beira” Hospital Center were selected for the study. The study consisted of 929 patients submitted to elective surgery between September 2008 and July 2010. A total of 71.3 % were on chronic medication. The mean number of drugs taken was 2.4 ± 2.5(1-14). In logistic regression analysis both taking chronic medication and withdrawing it were not risk factors for the occurrence of adverse events.This work provides evidence that chronic medication and its management, either continuing or the withdrawal of it, may not add significant risk to perioperative period.

Anti-proteinuric effect of sulodexide in adriamycin-induced nephropathy rats

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 This study investigated the anti-proteinuric effect of sulodexide in rats with adriamycin (ADR) nephropathy. A total of 40 healthy male Sprague-Dawley (SD) rats were randomly assigned to four groups: normal control group (Control-group), ADR control group (ADR-group), sulodexide treatment group (SUL-group), and losartan treatment group (LOS-group). The ADR-induced rat models were established by injecting two different doses of ADR (4 and 3.5 mg/kg) into the caudal vein of rat for two consecutive weeks. After that, SUL-group and LOS-group were respectively treated with sulodexide (10 mg/kg/day) and losartan (10 mg/kg/day) for an additional 4 weeks period. Samples of 24-hour urine were harvested at 3, 4, 5, and 6 weeks after the model establishment. The pathological change in renal tissues was observed by light microscopy, the function of liver and kidney were assayed at week 6th . The results showed that the urinary excretion of protein progressively increased in ADR-group, and accompanied with severe nephrotic syndrome such as massive albuminuria, proteinuria, and hyperlipidemia. Sulodexide effectively reduced the 24-hour urinary protein excretion of ADR-induced nephropathy rats, preventing focal segmental glomerulosclerosis. There was no significant difference between LOS-group and SULgroup for reducing urinary protein excretion (P < 0.05). Sulodexide alleviated ADR-induced nephrotoxicity as good as losartan in a short period of treatment.

Assessment of the knowledge, behavior and practice of self-medication amongst female students in a pakistani university

2013-01-04T02:01:50Z

Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 This study set sights at the issue of predominance of the attitude and behavior of self medication, medication storage and self treatment among female students of a Pakistani university. Random sampling and cross sectional surveys were conducted after collecting the data with the help of a questionnaire that was circulated amongst students. Of the 450 participants, 78.74 % of students admitted that they store medicines with them while other 50.95 % of students replied that they stop taking medicine prescribed by their doctors with the doctor’s intimation. The 78.74 % females were involved in self-medication. The 21.98 % were of the opinion that they did it to save their time and the 12.57 % claimed that the medicine given by the doctor did not have any effect. The medicines which are used to treat symptoms as self-medication are analgesics and antipyretics (22.57 %), ear, nose and throat drugs (14.34 %), vitamins and minerals (12.17 %), gastro-intestinal tract drugs (10.30 %), anti-infections (8.05 %) and herbal medicines (5.44 %). Female students should be educated to be sure to acquire safe practice by increasing their knowledge. Such strong policies should be instigated that the availability of unprescribed medicines should be restricted to avoid hazards due to self-medication.

Pharmacovigilance: assessment about the implantation and operation at pharmaceutical industry

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 This study aims to evaluate the implementation and operation of a pharmacovigilance program in the pharmaceutical industry in Brazil, taking as a tool a questionnaire with closed questions. The survey was carried out between the second quarter of 2009 and the first quarter of 2010. From 181 pharmaceutical companies that received the questionnaire, 7.18 % did not answer, but reported that they did not have a pharmacovigilance program or said that it was confidential company information, 27.62 % have contributed to the survey by answering the questions. Of these, 82 % said they already have a program of pharmacovigilance and 18 % said the program was under implementation. Moreover, companies considered small businesses represent the majority of which are in the deployment phase of their pharmacovigilance programs. Considering results and comparing with the number of notifications received on the reports from Sistema de Notificações em Vigilância Sanitária (Notifications System in Health Surveillance), it was observed that pharmaceutical companies represent a small portion when compared to hospitals and notifying pharmacies.

Evaluation of the effect of prednisolone on the inflammatory process and alveolar diameter in elastase- induced pulmonary emphysema in rats

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 This study evaluated the effect of prednisolone on acute lung inflammatory response, tissue damage and nitric oxide in elastase-induced emphysema in rats. A total of 32 male rats were divided into four groups: control and prednisolone groups received intratracheal instillation of saline; emphysema and emphysema + prednisolone groups received elastase. Prednisolone was administered in prednisolone and emphysema + prednisolone groups for 25 days by gavage. The results showed a significant increase in the alveolar airspace enlargement in the emphysema group. However, comparing control and emphysema + prednisolone groups, the treatment did not show significant reduction in the alveolar airspace enlargement. The number of leukocytes and nitric oxide level in BALF did not show statistically significant difference between groups. Despite widespread clinical use of corticosteroids in respiratory diseases, there was no direct protective effect on emphysema in treated animals, suggesting further studies related to its mechanism of action and on its clinical use in patients with emphysema.

Tailoring binary and tertiary solid dispersion compositions of nelfinavir using spray drying

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Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 In order to reduce the recrystallinity of poorly insoluble drug nelfinavir, PEG 6000 blends were prepared by spray drying with HPMC. The maximal reduction of recrystallinity in PEG 6000 was obtained by co-spray drying with HPMC as revealed by in vitro dissolution studies. The resulting ternary solid dispersions containing nelfinavir were characterized. The results of this study show that addition of PEG 6000 to nelfinavir/HPMC system leads to extended release of nelfinavir that in most cases recrystallizes indicated by reduction in solubility. For all ternary dispersions containing 20 % of nelfinavir, the drug was highly amorphous and dissolution was improved compared to binary 20/80 w/w nelfinavir/HPMC solid dispersion. For all ternary dispersions containing 40 % of nelfinavir, the drug indicated slower and consistent release over a prolonged time, without recrystallization. These results show that provided nelfinavir is highly amorphous, addition of PEG 6000 to HPMC leads to an extension of drug release.

Antibacterial activity and toxicity of drimys brasiliensis

2013-01-04T02:01:50Z

Articulo Latin American Journal of Pharmacy; vol. 31, no. 7 Men have used medicinal plant properties to treat infectious diseases. Both the rise of emerging infectious diseases as the microbial resistance problem has stimulated the searching for new antimicrobial agents. This study evaluated the antibacterial activity and toxicity of crude extracts, fractions and pure compounds from Drimys brasiliensis. The antibacterial activity of five extracts, twelve fractions and five isolated compounds were tested against six Gram-positive and seven Gram-negative bacteria. The methodology used was agar dilution. The extract potential toxicities were evaluated using Artemia salina assay. Antibacterial activity tests showed some promising results, such as bark chloroform extract with minimum inhibitory concentration (MIC) of 62.5 μg/mL for Bacillus cereus, fraction G2 with MIC for Staphylococcus aureus of 62.5 μg/mL, and methoxy-polygodial compound with MIC to Bacillus cereus of 31.25 μg/mL. There was no activity against Gram-negative bacteria. The bark dichloromethane extract showed MIC of 1000 μg/mL against Helicobacter pylori. The best results corresponded to fractions E and G2, with a MIC of 500 μg/mL. Among the isolated compounds, polygodial showed better activity with MIC of 250 μg/mL. Artemia salina tests showed that the bark dichloromethane extract and the fractions E and G2 showed toxicity, with LC50 values of 27.51, 25.29 and 139.7 μg/mL, respectively. The results showed the antibacterial activity of Drimys brasiliensis, with potential toxicity, but with possible antimutagenic action.

Determination of dezocine in rabbit plasma by liquid chromatography-mass spectrometry and its application

2013-01-04T02:01:48Z

Comunicacion Latin American Journal of Pharmacy; vol. 31, no. 6 A sensitive and selective liquid chromatography-mass spectrometry (LC–MS) method for determination of dezocine in rabbit plasma was developed and validated. After addition of diazepam as internal standard (IS), liquid–liquid extraction (LLE) was used for sample preparation, and chromatography involved Agilent SB-C18 column (2.1 mmx50 mm, 3.5 um) using 0.1 % formic acid in water and acetonitrile as a mobile phase with gradient elution. Detection involved positive ion mode electrospray ionization (ESI), and selective ion monitoring (SIM) mode was used for quantification of target fragment ions m/z 245.8 for dezocine and m/z 284.8 for diazepam (internal standard, IS). The assay was linear over the range of 5–500 ng/mL for dezocine, with a lower limit of quantitation (LLOQ) of 5 ng/mL for dezocine. Intra- and inter-day precisions were less than 13 % and the accuracies were in the range of 93.1-105.2 % for dezocine. This developed method was successfully applied for the determination of dezocine in rabbit plasma for pharmacokinetic study.

Propofol exhibits inhibitory effect towards human liver microsomes (HLMs)- catalyzed glucuronidation of thienorphine

2013-01-04T02:01:48Z

Comunicacion Latin American Journal of Pharmacy; vol. 31, no. 6 Drug-drug interaction (DDI) is a challenging problem in the process of drug utilization. Inhibition of glucuronidation reaction of drugs is a major reason for DDI. The aim of the present study is to predict propofol-thienorphine interaction from the perspective of propofol’s inhibition towards thienorphine glucuronidation. The human liver microsomes (HLMs) incubation system supplemented with uridine 5’-diphosphoglucuronic acid (UDPGA) was used. The results showed that propofol inhibited HLMscatalyzed thienorphine glucuronidation in a concentration-dependent manner. Both Dixon plot and Lineweaver-Burk plot showed that the inhibition of thienorphine glucuronidation by propofol was best fit to competitive inhibition, and the second plot using slopes from Lineweaver-Burk plot versus thienorphine concentration was used to determine the inhibition kinetic parameter (Ki ) value to be 365.9 μM. Whether the in vitro inhibition of propofol towards thienorphine glucuronidation can induce the in vivo propofolthienorphine interaction might be influenced by many factors, including various pharmacokinetic factors influencing the in vivo concentration of propofol. These data should be carefully explained due to complicated factors influencing the in vitro-in vivo extrapolation (IVIVE) results.