Bioequivalence study of a single 150-mg dose of two intramuscular netilmicin products in Thai healthy volunteers.

Objective: Netilmicin, a broad-spectrum semisynthetic aminoglycoside antibiotic, is used in the treatment of a wide variety of bacterial infections. The purpose of this study is to compare the bioavailability of two products of 150 mg netilmicin by intramuscular administration in Thai healthy volunteers: The generic drug is Nelin® (test; Biolab Co., Ltd., Thailand) will be called “Test” and Netromycin® (reference; Schering-Plough Ltd., USA) will be called “Reference”. Methods: A single-dose, 2-treatment, 2-period, 2-sequence, randomized crossover study was conducted in 24 healthy Thai volunteers. Each volunteer received a 150 mg intramuscular injection of the reference or test drugs. Blood samples were collected before dosing and at various time points up to 48 hours after dosing and analyzed for netilmicin concentrations using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. The pharmacokinetic parameters including Cmax, AUC0-t, AUC0-¥, Tmax and t1/2 were analyzed using the non-compartmental model. Drug safety and tolerability were assessed. Results: Twenty-four volunteers completed both treatment periods. The geometric mean ratios (test/reference) between the two products of netilmicin were 100.30% (90% CI, 88.02%-114.28%) for Cmax, 94.94% (90% CI, 88.94%-101.34%) for AUC0-t, and 94.88% (90% CI, 88.85%-101.32%) for AUC0-¥. There was no significant difference of the Tmax values between the two studied products (P>0.05). No adverse events related to the study drugs were found. Conclusion: The two products of intramuscular netilmicin are bioequivalent. Both products are well tolerated.

Risk of breast cancer in post-menopausal women using hormone replacement therapy.

OBJECTIVE: To study the relationship of hormone replacement therapy (HRT) in post-menopausal women and risk of breast cancer. PATIENTS AND METHOD: The authors conducted a case-control study comparing the proportion of HRT used between breast cancer and non-breast-cancer women. Cases were breast cancer patients who had natural menopause (excluded hysterectomy) and aged > or = 50-years-old from the Siriraj Breast Cancer database (1983-1996). Controls were post-menopausal volunteers aged 50 year or older who visited Siriraj Hospital for other purposes such as elderly clinics, health check, etc. After informed consent, well-trained surgeons examined the women in the control group to exclude any potential breast cancer. Patient characteristics and risk factors were collected. RESULTS: Of 1,913 patients in the database, 623 were included as the cases. Data from 679 volunteers were collected for controls from May to December 1999. Among 1,302 of the study population 58 women had ever used HRT (4.5%), which distributed to 3.2 per cent (20/623) in cases and 5.6 per cent (38/679) in controls. From univariate analysis, age, age at menopause, number of children, habitat, education, contraceptive pills, familial history of breast cancer and HRT usage were associated with breast cancer (p-value<0.05). After multivariate forward stepwise logistic regression analysis, there was no association between HRT use and breast cancer (adjusted odds ratio (OR) = 0.61, 95% CI = 0.31-1.20). In subgroups analysis, women who had older age, higher education level, history of taking contraceptive pills, or positive familial history of breast cancer in second degree relatives had a decreased risk of breast cancer, while those living outside Bangkok had an increased risk. CONCLUSION: Hormonal replacement therapy in post-menopausal women was not associated with increased risk of breast cancer.

The side effects of non-steroidal anti-inflammatory drugs: Are they attributed to the selective inhibition of different isoforms of cyclo-oxygenase.

Cyclooxygenase (COX)exists as two isoforms. Cox-1 in present under physiological conditions and COX-2 is induced by inflammatory stimuli. Previous studies in vitro have suggested that the side-effects of non-steroidal anti-inflammatory drugs (NSAIDs) correlate with their ability to inhibit COX-1, while the anti-inflammatory effects are due to their ability to inhibit COX-2 In order to strengthen this hypothesis, we examined the correlation between the inhibitory effects of eight NSAIDs (ibuprofen, aspirin, diclofenac, sulindac, naproxen, indomethacin, tolmetin and piroxicam) on the activity of COX isoforms in vitro and the range of relative risks of gastrointestinal (GI) complications that have been reported with individual NSAID in a meta-analysis. Analysis by Spearman rank correlation test demonstrated that IC50 complications (rs = 0.74, p < 0.05). A similar analysis using the IC50 of NSAIDs on the activity of COX-2 did not demonstrate any significant correlation (rs =- 0.59, p = 0.12). The ratio of COX-2/COX-1 did not appear to have any significant correlation with the risks of clinical GI side-effects (rs = 0.5, p = 0.21). Further analyses of in vitro data from other sources are encouraged to validate the usefulness of this model in predicting the GI side effects of each particular NSAID.

Development of Thai quality-of-life questionnaires for patients with chronic renal failure.

Chronic renal failure (CRF) is one of a number of major diseases that seriously affects quality-of-life (QOL). In this study, we developed a disease-specific QOL questionnaire in Thai for CRF. A list of items important to QOL of CRF patients was created by interviewing five patients, four nephrologists, and four nephrology nurses to identity items that affect patients’ QOL. Additional items were sought from English questionnaires. Another 50 CRF patients were then interviewed to determine the importance of each item by rating then on a scale of 1 (minimally important) to 5 (extremely important). Patients were also encouraged to add items which were not on the list. For each potential item, a frequency-importance score was calculated by adding each patient’s score. A combination of factor analysis and clinical judgment was then used to develop the final questionnaire, with questions scored on the 5-point Likert scale (ranging from “none of the time” to “all of the time”). Psychometric properties were subsequently evaluated in CRF patients at Siriraj Hospital. The validity of the questionnaire was assessed using the relationship between QOL questionnaire scores and the severity chronic renal failure assessed by the adequacy of dialysis diochemical parameters such as serum albumin, urea and creatinine and nurses’ or patients’ global assessment. Reproducibility and internal consistency were examined twice by interviewing 40 hemodialysis patients who came to hemodialysis clinic and had follow-up one week later. The final questionnaire consisted of 24 questions in five domains (physical symptoms, fatigue, psychological, social and emotional). The scores for all corrected strongly with nurses’ and patients’ assessment scores. The reproducibility of the questionnaire was high (intraclass correlation coefficient between 0.60 and 1.00 for the five domains except for the social domain). A high internal consistency in the questionnaire was found using the o-coefficient of Cronbach (ranging between 0.50-0.86 for the two tests). This questionnaire appears to be valid and reliable for assessing CRF patients.

The bioequivalence of generic and original drugs: An in vitro study.

We compare the bioequivalence of selected original and generic drugs which were dispensed in Siriraj Hospital in 1994. The 14 items which consist of 7 local and 7 original drugs were chosen on the basis of volume of consumption and price differentials. The in vitro equivalence studies used were assay, weight variation, content uniformity, dissolution test and/or disintregration test. Tested samples of the two groups were Sorbitrate vs. Isotrat 20 mg, Lopid vs. Hidil 300 mg, Nolvades-D vs. Tamoplex 20 mg, Sibilium vs. Flunazine 5 mg, Adalat vs. Nelapine 5 mg, Herbesser vs. Dilatam 30 mg and Tarivid vs. Occidal 100 mg. This study demonstrated no difference of the in vitro test of local and original drugs, suggesting comparable quality of generics to originals.

Articles published by staffs of faculty of medicine Siriraj Hospital during 1992-1995.

Articles published by faculty staffs during 1992-1995 in various journals were collected and analysed. Total number of the articles published during the 4-year period was 1,387 articles. Four hundred and twenty-five, 446, 295, and 221 articles were published in 1992, 1993, 1994 and 1995 respectively or 0.66, 0.69, 0.46 and 0.34 article per person per year. On average, clinical departments published more articles than preclinical departments. Her Majesty’s Cardiac Centre, Department of Pediatrics, Department of Medicine, Department of Dermatology, department of Blood Transfusion and Medicine and Department of Microbiology published more than one article per person per year. The most common journal that published articles of the faculty staffs was Siriraj Hospital Gazette. The top three peer-reviewed journals that published articles from the faculty staff, were Journal of the Medical Association of Thailand, Southeast Asian Journal of Tropical Medicine and Public Health and Asian Pacific Journal of Allergy and Immunology. Department of Medicine, Department of Pediatrics and Department of Orthopaedics and Rehabilitation contributed for 20.5, 10.6 and 9.1 percents of the publications in these journals respectively.