AimsTo assess the pharmacokinetic and pharmacodynamic effects of co-administration of a combined oral contraceptive (ethinyloestradiol plus levonorgestrel) and lamotrig ine. MethodsOver a period of 130 days, healthy female subjects took lamotrigine (titrated up to 300 mg day − 1 ) and the combined oral contraceptive, either individually or as cotherapy. Plasma ethinyloestradiol and levonorgestrel concentrations were measured in the presence and absence of lamotrigine, and serum lamotrigine concentrations were measured in the presence and absence of the combined oral contraceptive. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone, oestradiol and sex hormone binding globulin were also determined. ResultsOf the 22 enrolled subjects, 16 had evaluable pharmacokinetic data. The mean (90% CI) ratios of lamotrigine area under the concentration-time curve from 0 to 24 h (AUC(0,24 h)) and maximum observed concentration ( C max ) of lamotrigine when it was given with the combined oral contraceptive and during monotherapy were 0.48 (0.44, 0.53) and 0.61 (0.57, 0.66), respectively. Ethinyloestradiol pharmacokinetics were unchanged by lamotrigine, the mean combined oral contraceptive + lamotrigine : combined oral contraceptive alone ratios (90% CI) of the AUC(0,24 h) and C max of levonorgestrel were 0.81 (0.76, 0.86) and 0.88 (0.82, 0.93), respectively. FSH and LH concentrations were increased (by 4.7-fold and 3.4-fold, respectively) in the presence of lamotrigine, but the low serum progesterone concentrations suggested that suppression of ovulation was maintained. Intermenstrual bleeding was reported by 7/22 (32%) of subjects during co-administration of lamotrigine and combined oral contraceptive. ConclusionsA clinically relevant pharmacokinetic interaction was observed during co-administration of a combined oral contraceptive and lamotrigine. A dosage adjustment for lamotrigine may need to be considered when these agents are co-administered. A modest decrease in the plasma concentration of levonorgestrel was also observed but there was no corresponding hormonal evidence of ovulation. Jagdev Sidhu et al. 19261 :2 Br J Clin Pharmacol

SUMMARY BackgroundSymptoms of gastro-oesophageal reflux disease (GERD) may persist despite daily treatment with a proton pump inhibitor (PPI).

BackgroundThe utility of intramuscular (IM) oxytocin for the prevention of postpartum hemorrhage in resource-poor settings is limited by the requirement for temperature-controlled storage and skilled staff to administer the injection. We evaluated the safety, tolerability and pharmacokinetics (PK) of a heat-stable, inhaled (IH) oxytocin formulation.MethodsThis phase 1, randomized, single-center, single-blind, dose-escalation, fixed-sequence study (NCT02542813) was conducted in healthy, premenopausal, non-pregnant, non-lactating women aged 18–45 years. Subjects initially received IM oxytocin 10 international units (IU) on day 1, IH placebo on day 2, and IH oxytocin 50 μg on day 3. Subjects were then randomized 4:1 using validated GSK internal software to IH placebo or ascending doses of IH oxytocin (200, 400, 600 μg). PK was assessed by comparing systemic exposure (maximum observed plasma concentration, area under the concentration-time curve, and plasma concentrations at 10 and 30 min post dose) for IH versus IM oxytocin. Adverse events (AEs), spirometry, laboratory tests, vital signs, electrocardiograms, physical examinations, and cardiac telemetry were assessed.FindingsSubjects were recruited between September 14, 2015 and October 12, 2015. Of the 16 subjects randomized following initial dosing, 15 (IH placebo n = 3; IH oxytocin n = 12) completed the study. IH (all doses) and IM oxytocin PK profiles were comparable in shape. However, systemic exposure with IH oxytocin 400 μg most closely matched IM oxytocin 10 IU. Systemic exposure was approximately dose proportional for IH oxytocin. No serious AEs were reported. No clinically significant findings were observed for any safety parameters.InterpretationThese data suggest that similar oxytocin systemic exposure can be achieved with IM and IH administration routes, and no safety concerns were identified with either route. The inhalation route may offer the opportunity to increase access to oxytocin for women giving birth in resource-poor settings.

INTRODUCTION:Surgical site infection (SSI) is defined as infection occurring in an incisional wound within 30 days of the procedure or within 1 year if a prosthesis is implanted. A few studies have reported a relationship between low serum albumin level and low cholesterol level in surgical site infection, length of hospital stay and death and is reported to be one of the major causes of morbidity and mortality among hospitalized patients. METHOD:1 year prospective cohort study was conducted in Tertiary Health care Centre, Indore. A study population of 248 patients from hospital admitted in Department of General Surgery for elective operation. RESULT:From Total Patients - 172 (69.4%) were male patients and 76 (30.6%) were female patients. The frequency of patients developed SSI in hypoalbuminemia was 25(44.6%) in number compare to n=18(10.7%) in normal and to n= 03(12.5%) in hyper albuminemia. The Relative Risk between Hypoalbuminemia and SSI is 4.17 with CI (2.46  to 7) (P = <0.001). There is a significant association between cholesterol levels and the occurrence of SSI, with majority of the people with SSI had Hypocholesterolemia and it was found to be statistically significant with Relative risk(RR=3.98, CI= 2.28 to 6.95) (P = <0.001). CONCLUSION:Low blood cholesterol and albumin level are the important factors which is usually can lead to significant decrease in this preventable post operative complications especially in a malnourished population presenting in a government setup.