The effect of nutritional status on the pharmacokinetic profile of acetaminophen.

Nutritional imbalance (low protein / high fat) is a public health problem affecting many people in developing and developed nations. Such an imbalance will influence pathophysiological homeostasis in individuals and thereby considerably impact drug pharmacokinetics. It was reported that short-term fasting increases acetaminophen exposure in healthy subjects, whereas no effect was observed after a high-fat diet. These findings suggest the necessity of considering nutritional status when assessing the risk of acetaminophen-induced hepatotoxicity. Additionally, the role of nutrition status on the pharmacokinetic profile of acetaminophen (APAP) at toxic doses is either scanty or not available. With this background, we aimed to compare the effects of nutrition status on the pharmacokinetic profile of APAP at a toxic dose in three different dietary regimens like - Normal diet (ND), Low protein diet (LPD), and High-fat diet (HFD). Balb/C female mice were divided into three groups after weaning, and for the next 15 weeks, they were fed with their respective diets (ND, LPD, and HFD). After that, mice were dosed with APAP (300 mg/kg p.o), and blood sampling was done at different time intervals and centrifuged at 3000 rpm for 5 min to collect plasma samples. Plasma samples were analyzed using the HPLC method. Data analysis was done by Non-compartment analysis using Phoenix WinNonlin 8.3 software. LPD group shows higher values of Cmax, tmax, t1/2, and AUC0-4, AUC0-x values than ND and HFD groups. Both Cmax and AUC follow the pattern of drug exposure where LPD > ND > HFD. In conclusion, nutrition in the diet alters APAP pharmacokinetic profile at a toxic dose in three different diet regimes. Further study on CYP450 concentration and activity is essential to understand the pharmacokinetics difference between these dietary regimens.

Evaluation of Supportive Care Management Outcomes in Cancer Chemotherapy: A Prospective Observational Study in a Tertiary Care Teaching Hospital in South India.

AIMS: Evaluation of supportive care management of cancer patients experiencing drug-related problems (DRPs) is a challenge because it might increase the cost due to additional therapy. The main objectives of this study were to estimate chemotherapy-associated drug-related hospital admissions in the department of medical oncology and to estimate the cost of managing chemotherapy-associated DRPs. SETTINGS AND DESIGN: This study is a prospective observational study. SUBJECTS AND METHODS: Patients with chemotherapy-related DRPs were prospectively identified from the patient's medical records. The contribution of DRPs and cost incurred due to each hospitalization was assessed. STATISTICAL ANALYSIS USED: Data were analyzed using SPSS® 20.0 version. RESULTS: Out of 55 patients analyzed for DRPs, 25 (45.5%) patients in the age group of 51-60 years experienced DRPs most frequently. Most commonly occurring DRP was adverse drug reactions 42 (76.4%), which were more frequent in females. DRPs were maximum with alkylating agents 15 (27.3%) and the least with hormonal agents 1 (1.8%). The mean length of hospitalization was 9.6 ± 6.5 days. The total direct medical cost was Rs. 31,540 ± 42,476, of which medicine cost accounted for Rs. 16,550 ± 25,404, constituting a major share of the total medical costs. CONCLUSIONS: Pharmacists can provide better patient care by identifying and preventing DRPs and reducing drug-related morbidity and mortality.

Effectiveness of clinical pharmacist intervention on health-related quality of life in chronic obstructive pulmonary disorder patients - a randomized controlled study.

WHAT IS KNOWN AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD), a preventable and treatable disease, has been described as '10% medication and 90% education'. Extreme physician scarcity limits the implementation of quality healthcare delivery in India. We conducted this study to evaluate the effectiveness of clinical pharmacist intervention on health-related quality of life (HRQoL) in patients with COPD in an Indian tertiary care hospital. METHODS: An open-labelled randomized controlled study was conducted over a 3-year period, at Kasturba Medical College Hospital, Manipal, India, after obtaining institutional ethics clearance (IEC 88/2012). The study was registered with the Indian clinical trial registry (CTRI/2014/08/004848). Patients were randomly assigned to two groups (intervention group [IG] and control group [CG]) by envelope method. St. George's Respiratory Questionnaire (SGRQ) was used to assess the HRQoL. The pharmacist intervention laid emphasis on (i) importance of medication compliance, (ii) need for smoking cessation, (iii) simple exercise, (iv) proper use of inhaler devices and (v) need for timely follow-up by pulmonary medicine department. SGRQ assessment was repeated at 6, 12, 18 and 24 months. RESULTS: Of 328 patients with COPD screened during the study period (March 2012 to June 2013), 260 (79%) were recruited. Of these, 202 (78%) patients completed follow-up (98 in CG and 104 in IG). Both groups were matched for baseline, sociodemographics and clinical characteristics. SGRQ scores and its subscales (symptoms, activity and impact) improved significantly after the pharmacist intervention in IG at follow-up (P < 0·001). WHAT IS NEW AND CONCLUSION: Our randomized controlled study shows that pharmacist intervention improved the HRQoL of patients with COPD in India. The generalizability of our results requires exploration even within other settings in India. Nonetheless, our results provide support for a greater involvement of pharmacists in the care of patients with COPD.

Assessment of cost of illness for diabetic patients in South Indian tertiary care hospital.

BACKGROUND: The impact of diabetes on health-care expenditures has been increasingly recognized. To formulate an effective health planning and resource allocation, it is important to determine economic burden. OBJECTIVE: The objective of this study is to assess the cost of illness (COI) for diabetic inpatients with or without complications. METHODOLOGY: The study was conducted in the medicine wards of tertiary care hospital after ethical approval by the Institutional Ethical Committee. A total of 116 each diabetic with or without complications were selected and relevant data were collected using COI questionnaire and data were analyzed using SPSS version 20. Mann-Whitney U test is used to assess the statistical significant difference in the cost of treatment of diabetes alone and with complications'. P ≤ 0.05 was considered statistically significant. RESULTS: Total COI includes the cost of treatment, investigation, consultation fee, intervention cost, transportation, days lost due to work, and hospitalization. The median of total COI for diabetic care without any complication was Rs. 22,456.97/- per patient per annum and with complication was Rs. 30,634.45/-. Patients on dialysis had to spend 7.3 times higher, and patients with cardiac intervention had to spend 7.4 times higher than diabetic patients without any complication. CONCLUSION: Treatment costs were many times higher in patients with complications and with cardiac and renal interventions. Complications in diabetic patients will increase the economic burden to family and also to the society.

Impact of diabetic foot ulcer on health-related quality of life: A cross-sectional study.

Studies have reported that health-related quality of life (HRQoL) is adversely affected by diabetic foot ulcer (DFU). There is a paucity of data on the effects of foot ulcers on HRQoL of diabetes patients in our population. Because South-Asians, especially Indians, have unique features related to diabetes and its complications, generalizing the data about their effect on HRQoL from any other part of the world is not a pragmatic approach. This study evaluated the impact of foot ulcers on HRQoL of diabetes patients. This cross-sectional study, conducted in Kasturba Hospital, Manipal (coastal South India), included 200 DFU patients in a study group (SG) and 200 diabetes patients in a control group (CG). The RAND-36 questionnaire was employed for evaluating HRQoL scores for the patients in both groups. DFU patients also completed the Diabetic Foot Ulcer Scale-Short Form questionnaire. Independent t-test was used to test the differences in mean scores. Results found that both CG and SG have "poor" HRQoL (mean score <50) on all the subscales except for two in CG. There is a statistically significant difference between groups (P < 0.05) on all eight of the subscales of HRQoL. For both CG and SG, the Physical Component Summary domain score (44.9 ± 6.3 v 28.4 ± 3.4) and Mental Component Summary domain score (42.5 ± 3.8 v 29.5 ± 7.1) were poor. There were significant differences between CG and SG for both mean Physical Component Summary score and Mental Component Summary score of HRQoL (p < 0.05). The Diabetic Foot Ulcer Scale-Short Form found that HRQoL is very poor for DFU patients on all six domains. The study concludes that DFU patients have very poor HRQoL compared with diabetic patients. Likewise, the diabetic foot is associated with severely impaired HRQoL in both physical and mental health aspects. This study will help to develop a patient education model for DFU patients by looking at the various HRQoL domains that are adversely affected by the presence of foot ulcer.

Topical application/formulation of probiotics: will it be a novel treatment approach for diabetic foot ulcer?

Treatment of chronic conditions like diabetic foot ulcer (DFU) is challenging due to increased susceptibility for infection and delayed wound healing. Complexity of existing therapy, adverse effects and microbial resistance emphasizes the need of an alternative approach for the management of DFU. The increasing body of evidence associated with probiotic application in diverse disease states merits its use in wound healing and infection too. Different probiotic strains have shown their efficacy in various infections like gut infections, oral infections and urogenital infections. Experimental studies have demonstrated probiotics' ability for gastric ulcer healing. Underlying mechanism of the above therapeutic effects of probiotics involves modulation of local and systemic immunity. The hypothesis is based on the concept that mechanism of anti-infective and ulcer healing action of probiotics will be similar in peripheral wounds and ulcers as on any other part of the body. This paper focuses on the hypothesis that topical applications/formulation of probiotics may be effective for the treatment of diabetic foot ulcers.

Investigation of nano lipid vesicles of methotrexate for anti-rheumatoid activity.

BACKGROUND: The purpose of this study was to formulate and evaluate nano lipid vesicles of methotrexate (MTX) for its anti-rheumatoid activity. METHODS: In this study the principle of both active as well as passive targeting using MTX-loaded stealth liposomes as per the magic gun approach was followed. Stealth liposomes of MTX were prepared by thin-film hydration method using a PEGylated phospholipid-like DSPE-MPEG 2000. Similarly, conventional liposomes were prepared using phospholipids like DPPC and DSPC. Conventional liposomes were coated with a hydrophilic biocompatible polymer like chitosan. They were investigated for their physical properties and in vitro release profile. Further, in vivo screening of the formulations for their anti-rheumatoid efficacy was carried out in rats. Rheumatoid arthritis was induced in male Wistar-Lewis rats using complete Freund's adjuvant (1 mg/mL Mycobacterium tuberculosis, heat killed in mineral oil). RESULTS: It was found that chitosan coating of the conventional liposomes increased the physical stability of the liposomal suspension as well as its entrapment efficiency. The size of the unsonicated lipid vesicles was found to be in the range of 8-10 µm, and the sonicated lipid vesicles in the range of 210-260 nm, with good polydispersity index. Further, chitosan-coated conventional liposomes and the PEGylated liposomes released the drug for a prolonged period of time, compared to the uncoated conventional liposomes. It was found that there was a significant reduction in edema volume in the rat group administered with the test stealth liposomal formulations and chitosan-coated conventional liposomes (PEGylated and chitosan-coated conventional) compared to that of the control and standard (administered with free MTX) group of rats. PEGylated liposomes showed almost equal efficacy as that of the chitosan-coated conventional liposomes. CONCLUSION: Lipid nano vesicles of MTX can be administered by intravenous route, whereby the drug selectively reaches the target site with reduced toxicity to other organs.

In vitro and in vivo evaluation of chitosan buccal films of ondansetron hydrochloride.

Buccal films of ondanstron hydrochloride were fabricated from mucoadhesive polymer, chitosan, and polyvinyl pyrrolidone (PVP K30) for the purpose of prolonging drug release and improving its bioavailability. All fabricated film formulations prepared were smooth and translucent, with good flexibility. The weight and thickness of all the formulations were found to be uniform. Drug content in the films ranged from 98 - 99%, indicating favorable drug loading and uniformity. The inclusion of PVP K30, a hydrophilic polymer, significantly reduced the bioadhesive strength and in vitro mucoadhesion time of the films, although the degree of swelling increased. In vitro drug release studies in simulated saliva showed a prolonged release of over five to six hours for all formulations, except C4, with 99.98% release in 1.5 hours. Kinetic analysis of the release data indicated that the best fit model with the highest correlation coefficient for all formulations was the Peppas model. In vivo studies, on selected films in rabbits, were conducted, to determine the pharmacokinetic parameters such as C(max), T(max), and AUC(0-∞), using model-independent methods with nonlinear least-squares regression analysis. The AUC and values of C(max) of ondansetron hydrochloride were found to be significantly greater (P < 0.005) than the selected films C2 and C3, as compared to those from the oral solution, thereby confirming improved bioavailability via the buccal route. The T(max) values were also significantly greater (P < 0.005), indicating the slower release of the drug from buccal films, thereby, providing prolonged effects. Good in vitro-in vivo correlation was observed with R(2) values exceeding 0.98, when the percentage of drug released was correlated with the percentage of drug absorbed.

Evaluation of estrogenic activity of alcoholic extract of rhizomes of Curculigo orchioides.

The rhizomes of Curculigo orchioides Gaertn. (Amaryllidacea) is an important Ayurvedic as well as Unani drug. It is present in several drug formulations used in the treatment of menorrhagia and other gynecological problems. In this study, we conducted a comparative study of estrogenic activity of alcoholic extract of Curculigo orchioides with diethylstilbestrol in bilaterally ovariectomized young albino rats. Bilaterally ovariectomized albino rats were divided into five groups (n=9) receiving different treatments, consisting of vehicle (0.6% w/v sodium carboxy methyl cellulose), ethanolic extract of rhizomes of Curculigo orchioides at three different doses (viz., 300, 600, 1200 mg/kg body weight) and standard drug diethylstilbestrol (DES) at a dose of 2 mg/kg body weight. All these were administered orally daily for 7 days. Estrogenic activity was assessed by taking percentage vaginal cornification, uterine wet weight, uterine glycogen content and uterine histology as parameters of assessment. Alcoholic extract of Curculigo orchioides showed a significant increase in percentage vaginal cornification, uterine wet weight (P<0.001), uterine glycogen content (P<0.001) and a proliferative changes in uterine endometrium compared to the control.