Assessment of bioequivalence after subcutaneous and intramuscular administration of urinary gonadotrophins

The objective was to demonstrate bioequivalence between s.c. and i.m. administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio 3:1). In two randomized, single-centre, cross-over studies, 18 healthy volunteers on each formulation were assigned to one of the two administration sequences. Subjects were given single doses of one of the above gonadotrophins after endogenous gonadotrophin production had first been suppressed using high-dose oral contraceptive. Subsequently, rate (Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax and AUC, analysis of variance (ANOVA) was performed on log-transformed data and for tmax ANOVA was performed on ranks. Intramuscular and s.c. injections of Humegon were bioequivalent with respect to the main pharmacokinetic parameters, being AUC and Cmax of FSH absorption. Intramuscular and s.c. injections of Normegon were bioequivalent with respect to the AUC of FSH and not bioequivalent with respect to the Cmax of FSH. For tmax of FSH as well as for most LH variables of both preparations, bioequivalence could not be proven due to the high intra- and interindividual variability and/or concentrations being close to the detection limit. Thus, the main pharmacokinetic FSH variables after i.m. and s.c. administration of Humegon and Normegon were bioequivalent.      

The selectivity of different external binding sites for quaternary ammonium ions in cloned potassium channels

Tetraethylammonium (TEA) is thought to be the most effective quaternary ammonium (QA) ion blocker at the external site of K⁺ channels, and small changes to the TEA ion reduce its potency. To examine the properties of the external QA receptor, we applied a variety of QA ions to excised patches from human embryonic kidney cells or Xenopus oocytes transfected with the delayed rectifying K⁺ channels Kv 2.1 and Kv 3.1. In outside-out patches of Kv 3.1, the relative potencies were TEA > tetrapropylammonium (TPA) > tetrabutylammonium (TBA). In contrast to Kv 3.1, the relative potencies in Kv 2.1 were TBA > TEA > TPA. In Kv 3.1 and Kv 2.1, external tetrapentylammonium (TPeA) blocked K⁺ currents in a fast, reversible and, in contrast to TEA, time-dependent manner. The external binding of TPeA appeared to be voltage independent, unlike the effects of TPeA applied to inside-out patches. External n-alkyl-triethylammonium compounds (C₈, C₁₀ chain length) had a lower affinity than TEA in Kv 3.1, but a higher affinity than TEA in Kv 2.1. In Kv 3.1, the decrease in QA affinity was large when one or two methyl groups were substituted for ethyl groups in TEA, but minor when propyl groups replaced ethyl groups. Changes in the free energy of binding could be correlated to changes in the free energy of hydration of TEA derivatives calculated by continuum methodology. These results reveal a substantial hydrophobic component of external QA ion binding to Kv 2.1, and to a lesser degree to Kv 3.1, in addition to the generally accepted electrostatic interactions. The chain length of hydrophobic TEA derivatives affects the affinity for the hydrophobic binding site, whereas the hydropathy of QA ions determines the electrostatic interaction energy.     

High prevalence of type 2 diabetes in an urban settlement in Kerala, India

Background. Prevalence of type 2 or non insulin dependent diabetes mellitus is high among Indians living in India as well as abroad. Prevalence among persons of Indian origin in many countries is greater than that of people of other ethnic extraction. The Indian state of Kerala is distinguished by a high level of achievement in the health sector, characterised by both lower mortality rates and greater density of health care institutions that ensure access to most people. These attributes make the prevalence of diabetes and the pattern of its management in Kerala worth studying. Objective. To estimate the prevalence of diabetes among persons 20 years or older in an urban housing settlement in Trivandrum city, the capital of Kerala, as well as study the management of the disease in subjects affected. Design. Cross sectional survey for detecting diabetes and other chronic diseases in all willing residents of an urban housing settlement in Trivandrum, the capital city of Kerala, as part of a preventive campaign against lifestyle diseases. Fasting plasma glucose, serum triglycerides, cholesterol, height, weight and blood pressure were measured, and a detailed questionnaire administered to ascertain previous diabetic status and management. Results. Overall prevalence of type 2 diabetes is 16.3%. In the 30-64 age group, age standardised prevalence is 13.7%. Gender differences in prevalence are negligible. Greater prevalence is associated with advancing age, body mass index above 24.99, sedentary habits, serum total cholesterol > 239, serum triglycerides > 149, hypertension and smoking. Compared to non-diabetics, diabetics have greater mean and range of fasting plasma glucose values (8.87 + /-3.6 mM/l as against 4.34 + /-0.53 mM/l). 32 out of 38 diabetics among the subjects (82.4%) were already diagnosed even before the survey; of them, 89% were on medication. 3% of subjects had impaired fasting glucose, or FPG level between 110-125 mg/dl. Conclusion. Prevalence of type 2 diabetes among a group of urban residents in Trivandrum city in Kerala is very high. This is associated also with a high detection rate and compliance to treatment.