SUN-LB9 Pharmacokinetics of Sublingual Versus Oral Estradiol in Transgender Women

Sublingual administration of estradiol (E2) may be a safer and more effective hormone replacement therapy (HRT) route than oral estradiol, the most commonly used formulation, but it has yet to be investigated in transgender women. Unlike oral E2, sublingual E2 is thought to bypass the first pass effect by the liver, making it less likely to impact hepatic clotting factor synthesis, and thus decreasing the risk of thromboembolic events posed by oral administration, such as VTE and ischemic stroke (1). Additionally, studies in cisgender women have demonstrated a 13-fold higher peak serum concentration and a decreased estrone (E1) to estradiol ratio with sublingual administration, suggesting that sublingual E2 is more a physiologically potent route (2). To advance the understanding of sublingual E2 as an alternative method of administration in transgender HRT, we investigated the pharmacokinetics of estradiol when administered orally versus sublingually in transgender women. Ten transgender women naïve to estrogen were provided 1.0 mg of oral estradiol. Blood samples were collected via percutaneous intravenous catheter at baseline and at T=1,2,3,4,6, and 8 hours post-dosing. After a 7-day washout period, 1.0 mg of sublingual estradiol was dosed with identical sampling over time. Analysis of serum samples was performed using LC-MS/MS and estradiol immunoassay. Initial results demonstrate a higher peak serum concentration within 8 hours with sublingual dosing in both LC-MS/MS and immunoassay quantification (178±47 and 150±31 pg/mL, respectively) compared to oral administration (36±5 and 35±4 pg/mL, respectively; N=5). Peak concentration was reached at T=1 hour for sublingual E2 in both LC-MS/MS and immunoassay analysis, whereas oral E2 reached peak serum concentration at T=8 hours in LC-MS/MS analysis and T=6 hours in immunoassay analysis. Sublingual E2 still maintained higher overall mean concentrations of estradiol across the 8 hours compared to oral E2. Importantly, subjects reported high satisfaction with sublingual administration due to rapid dissolution (<2 minutes) and minimal taste; as a result, subjects predicted high ease of adherence in future HRT, which indicates the feasibility of sublingual E2 as an alternative to oral E2. Additional analysis of half-life and oral clearance will be performed at the completion of the study, in order to further establish pharmacokinetic differences and potency between the two routes. This pharmacokinetic data will allow future studies on optimal dosing, safety, and efficacy compared to oral estradiol in hormone replacement therapy. (1) Hembree et al. J Clin Endocrinol Metab. 2017;102(11):3869-3903. (2) Price et al., Obstet Gynecol. 1997.

EFFECT OF DIABETES MELLITUS ON RIFAMPICIN PEAK SERUM CONCENTRATION

<p><strong>Objective: </strong>To comparatively analyze the peak serum concentration (Cmax) of rifampicin and to determine the incidence of decreased Cmax between diabetic and non-diabetic adult pulmonary tuberculosis patients.</p><p><strong>Methods: </strong>A cross-sectional observational study was carried out in the chest and tuberculosis (TB) department of a tertiary care hospital after the approval of the institutional ethics committee. Five millilitre (ml) of blood was withdrawn by venipuncture from each patient at a time point of 2 h post dose administration at steady state concentration (C_ss). The separated serum was centrifuged at a rate of 3500 rotations per minute (rpm) for a period of fifteen minutes and the resultant serum was stored at-70 ° C until analysis. Estimation of rifampicin concentration was carried out in Thermo TSQ Ultra (MS/MS) with Shimadzu 20 AD UFLC LC-MS.</p><p><strong>Results: </strong>The mean (Standard Deviation (SD)) age of the study population was 46.8 (14.2) years. The mean serum C_max of rifampicin was significantly less in diabetic patients with pulmonary tuberculosis (p=0.0305).<strong> </strong>Statistically, a significant difference in the incidence of a decrease in C_maxwas found between diabetic and non-diabetic patients (p=0.0335). Diabetes mellitus was found to be the predominant factor that affects rifampicin C_max.</p><p><strong>Conclusion: </strong>In this study, an effect of diabetes mellitus (DM) on the peak serum concentration of rifampicin was observed. Patients with hyperglycemia levels had significantly reduced levels of rifampicin serum concentrations, thus showing an inversely proportional relationship between blood glucose and rifampicin serum levels.</p>

Amoxycillin for Parenteral Use: A Pharmacological and Clinical Evaluation

Pharmacological studies with intramuscular amoxycillin and intramuscular ampicillin were carried out in ten patients. Serum, urine levels, urinary recovery and renal clearance of intramuscular amoxycillin were similar to intramuscular ampicillin and to oral amoxycillin. The time to peak serum concentration was later for amoxycillin. Sputum levels were higher for amoxycillin. Amoxycillin intramuscularly was more painful than ampicillin in eleven out of thirty patients. The clinical response, evaluated in twenty-five patients was good and similar to ampicillin in our experience.

Effect of Iron and Calcium on Salicylazosulphapyridine Metabolism

Acute experiments involving a single dose of salicylazosulphapyridine (SASP) were performed in 5 volunteers. The peak serum concentration of SASP was found within 3 to 5 hours whereas for sulphapyridine derived from SASP it occurred at 12 to 24 hours. The addition of ferrous sulphate caused a significant decrease in the serum SASP concentration whereas the addition of calcium gluconate delayed the absorption of SASP without disturbing the degree of absorption. Total sulphapyridine concentration did not show any variation.