Safety evaluation of standardized Ayurvedic formulation-Panchvalkala, by subacute toxicity study.

ETHNOPHARMACOLOGICAL RELEVANCE: Panchvalkala is a conventional Ayurvedic medicine used as a douche in gynecological disorders such as leucorrhea, infertility, and endometriosis. Recently, we have reported the anticancer activity of Panchvalkala aqueous extract (PVaq) in cervical cancer cell lines, SiHa (HPV16+), HeLa (HPV18+), and mouse papilloma models. AIM OF THE STUDY: Here, we have evaluated the safety of the aqueous extract of Ayurvedic formulation, Panchvalkala (PVaq), in Swiss albino mice by performing subacute toxicity study. MATERIALS AND METHODS: Male and female Swiss albino mice (n = 5/sex/group) were gavaged orally with different doses of PVaq for 28 consecutive days. The mice were distributed into six groups: I (vehicle control), II (vehicle control reversal), III (PVaq 250 mg/kg), IV (PVaq 500 mg/kg), V (1000 mg/kg) and VI (1000 mg/kg high dose reversal). Animals were observed periodically to record any clinical signs of toxicity or mortality. After completion of treatment and recovery periods, animals were evaluated for the effect of PVaq on urine parameters, followed by hematological and biochemical parameters. Animals were sacrificed on day 29 for gross observation of vital organs and to study their histopathology. Reversal groups were maintained for further 14 days to observe any delayed onset of toxic side effects or reversal of toxicity, followed by sacrificing the mice on day 43. RESULTS: In the subacute toxicity study, PVaq did not show any significant change in food, water consumption, and body weights. There were no significant alterations in hematology, biochemistry, urine parameters, and histopathology of the analyzed tissues (brain, heart, liver, lung, spleen, thymus, kidney, epididymis/ovaries, and testis/uterus). The parameters were comparable to their respective controls in both the female as well as the male mice groups. Upon macroscopic and microscopic observation of vital organs, no abnormality was detected compared to the respective control groups. CONCLUSION: The subacute toxicity study demonstrated that oral administration of PVaq was safe in female and male Swiss albino mice.

Bioequivalence of generic and branded amoxicillin capsules in healthy human volunteers.

CONTEXT: The Medical Council of India urges doctors to prescribe generic drugs as far as possible. The Indian Medical Association had responded earlier saying that it requires guarantees on the quality of generic forms of drugs. Although no published scientific reports are available on the issue of therapeutic inequivalence, unconfirmed clinician accounts and newspaper reports of therapeutic inequivalence exist. AIM: This study was planned to ascertain whether bioequivalence of branded and generic amoxicillin capsule is comparable. SETTINGS AND DESIGN: An open-label, randomized, single-dose, two-treatment, two-sequence, two-period crossover oral bioequivalence study was conducted in 12 healthy, adult human subjects under fasting condition. MATERIALS AND METHODS: Serum samples, collected at 8 time points, were analyzed by a validated ultraviolet spectrophotometer method. Pharmacokinetic (PK) parameters such as area under the curve (AUC)0-t, AUC0-∞, Cmax, and Tmax were determined along with time above minimum inhibitory concentration (MIC). STATISTICAL ANALYSIS USED: The log-transformed PK parameters (Cmax, AUC0-t, AUC0-∞) were analyzed using a Two One-Sided Test ANOVA in SAS for each parameter. Tmax and MIC were analyzed by Wilcoxon rank-sum test in GraphPad Prism. RESULTS: Geometric mean ratio of Cmax fell within bioequivalence criteria. The upper and lower confidence limits of both AUC0-t and AUC0-∞ geometric mean ratio fell below bioequivalence criteria. Time above MIC of generic preparation was significantly lower than that of branded version. CONCLUSIONS: The generic capsule was not bioequivalent to the branded amoxicillin capsule.

Perception of pharmacovigilance among doctors in a tertiary care hospital: influence of an interventional lecture.

INTRODUCTION: One of the important pillars of an efficient pharmacovigilance system is contribution by healthcare professionals in the form of spontaneous reporting. This study was aimed at investigating the knowledge, attitude and practice of spontaneous ADR reporting among doctors in a teaching hospital in Pune, and to analyze the effect of an informative lecture about Pharmacovigilance on the same. METHODOLOGY: This was an interventional study conducted among 220 doctors at a tertiary care teaching hospital, Pune. Each participant was explained the purpose of study and asked to fill in a questionnaire about their knowledge, attitude and practice of pharmacovigilance. Only 80 of them attended the interventional lecture on Pharmacovigilance and again filled up the questionnaire after a period of one month from this intervention. RESULTS: Merely 7.5% of the participants knew ADR reporting system in India. Majority of the respondents (95%) knew that, as doctors, they could report ADRs but were unaware about the methodology to report (92.5%) which affected their practice of Pharmacovigilance. All (100%) the participants expressed that proper training should be provided to clinicians for ADR reporting & 81% felt ADR reporting should be made mandatory. Only 80 participants (36.4%) attended the interventional lecture which reflected a poor response. Intervention improved their (96%) knowledge about ADR reporting system and now majority of them (92%) agreed that all sort of ADRs should be reported (p < 0.001). CONCLUSION: Attitude towards ADR reporting was positive but knowledge about ADR reporting system was inadequate among doctors working in a teaching hospital in Pune. Education helped in improving knowledge and had an impact on attitude of participants regarding pharmacovigilance.

Experimental evaluation of anti-inflammatory effect of topical application of entada phaseoloides seeds as paste and ointment.

AIMS: The study was to study the anti-inflammatory effect of topical application of different formulations of seed pulp of entada phaseoloides. METHOD AND MATERIAL: After removing the shell, entada phaseoloides seeds were powdered. Paste was prepared with water and ointment with polyethylene glycol & Carbowax 3350. 32 Wister rats of either sex weighing 140-200 gram were divided into four groups, Group-I vehicle, Group-II entada phaseoloides paste, Group-III entada phaseoloides Ointment, Group-IV Diclofenac sodium Ointment. Arthritis was induced by injecting 0.1ml Complete Freund's adjuvant in sub plantar region of the left hind paw. Drug treatment was started on the same day and given for 12 days. Paw volume was measured with Plethysmometer on day 0, 1, 5, 12 and 21 for both the paws. Bodyweight and Gait was observed throughout the study. RESULTS: Localized inflammatory reaction developed in all the rats in 24 hours. In control group, there was no resolution of swelling even in 21 days. Both EP formulations showed significant (P < 0.001) anti-inflammatory activity as compared to control. entada phaseoloides ointment was equi-effective to that of Diclofenac sodium on 12(th) day. entada phaseoloides paste was significantly (P < 0.05) more effective than Diclofenac sodium on 21(st) day. CONCLUSION: Both the formulations of entada phaseoloides have anti-inflammatory activity and entada phaseoloides paste is significantly more effective than diclofenac sodium.

Effect of pretreatment with coenzyme Q10 on isoproterenol-induced cardiotoxicity and cardiac hypertrophy in rats.

BACKGROUND: Coenzyme Q10 (CoQ10) is a lipid-soluble, vitamin-like substance found in the hydrophobic interior of the phospholipid bilayer of most cellular membranes. It appears to be involved in the coordinated regulation between oxidative stress and antioxidant capacity of heart tissue when the heart is subjected to oxidative stress in various pathogenic conditions. OBJECTIVE: The objective of the present study was to investigate the effect of pretreatment with CoQ10 (100 mg/kg) on isoproterenol (ISO)-induced cardiotoxicity and cardiac hypertrophy in rats. METHODS: Albino male Wistar rats (250-300 g) were evenly divided by lottery method into 1 of the following 3 groups: the ISO group (olive oil 2 mL/kg orally for 18 days and ISO 1 mg/kg IP from days 9-18); the CoQ10 + ISO group (CoQ10 100 mg/kg orally for 18 days and ISO 1 mg/kg IP from days 9-18); and the control group (olive oil 2 mL/kg orally for 18 days and water IP from days 9-18). Twenty-four hours after the last dose of water or ISO, the rats were anesthetized and an ECG was recorded. Blood was withdrawn by retro-orbital puncture for estimation of serum creatine kinase-MB (CK-MB) isoenzyme levels, lactate dehydrogenase (LDH) levels, and aspartate aminotransferase activities. The animals were euthanized using an overdose of ether. The hearts of 6 animals from each group were used for estimation of superoxide dismutase (SOD) activity, reduced glutathione (GSH) concentration, lipid peroxidation (LPO), malondialdehyde (MDA), and total protein concentration. Histopathology of the 2 remaining hearts in each group was carried out by a blinded technician. RESULTS: A total of 24 rats (8 in each group) were used in this study; all rats survived to study end. Compared with the control group, the ISO-treated rats had a significant change in heart to body weight ratio (P < 0.001); significant changes in the endogenous antioxidants (ie, significantly higher myocardial MDA concentration [P < 0.001]; significantly lower myocardial GSH concentration [P < 0.001] and SOD activity [P < 0.01]); and significantly higher serum activities of marker enzymes (eg, CK-MB [P < 0.001] and LDH [P < 0.001]). Compared with the ISO group, the CoQ10 + ISO group had a significant change in heart to body weight ratio (P < 0.001); significant changes in the endogenous antioxidants (ie, significantly lower MDA concentration [P < 0.05]; significantly higher myocardial GSH concentration [P < 0.001] and SOD activity [P < 0.05]); and significantly lower serum activities of marker enzymes (eg, CK-MB [P < 0.05] and LDH [P < 0.01]). CONCLUSION: Pretreatment with CoQ10 (100 mg/kg) for 18 days was associated with moderate protection against ISO-induced cardiotoxicity and cardiac hypertrophy, and with lower myocardial injury by preserving endogenous antioxidants and reducing LPO in rat heart.