THE PHARMACOKINETICS OF 2 DOSES (50 µG AND 100 µG) LEVOTHYROXINE TREATMENT IN ATHYREOTIC PATIENTS

Objective: Hypothyroid has still be a problem in Thailand. Lack of pharmacokinetics information of levothyroxine in athyreotic patients for modify dosing. Therefore, the aim of this study was to investigate the pharmacokinetic parameters of 2 doses of levothyroxine(50 mg and 100 mg) in such group of patients. Methods: The 24 athyreotic patients were recruited and randomly assigned to receive 50 mg or 100 mg of levothyroxine. The pharmacokinetic parameters (Cmax, Tmax, AUC0-8, ke, T1/2 and Vd) of FT4 and TSH were calculated by the non-compartment model. The parameters of 2 doses were compared. Results: From the results found that, by monitoring FT4, there was no statistically significant difference (p>0.05) of almost all pharmacokinetic parameters between 2 doses except Cmax which has significant greater in 100 mg of levothyroxine. While all pharmacokinetics parameters of TSH were not statistically significant difference. The use of non-compartment model seems appropriate for calculation of pharmacokinetic parameters of FT4 (R2 = 0.81) while it has poor predictive capacity in terms of TSH (R2 = 0.24). Conclusion: In conclusion, administration of 50 mg and 100 mg of levothyroxine to athyreotic patients have similar pharmacokinetic in term of FT4(non-significant different in Tmax, AUC) and TSH. Further study of these parameters in more subjects is needed

PARAMETERS BETWEEN LOW AND HIGH DOSES OF PIOGLITAZONE IN TYPE 2 DIABETIC PATIENTS

Pioglitazone (PIO) is highly effective in decreasing blood glucose levels for type 2 diabetes mellitus (T2D), but it can induce serious adverse events such as edema and heart failure (HF). Some previous studies showed that the efficacy on glucose control and lipid levels was not related to the difference in doses of PIO in opposite to the incidence of edema which was doses-dependent of PIO. To compare glucose control, lipid control, adverse events, and pharmacokinetic (PK) parameters between low and high doses of PIO in T2D. Medical chart of 139 diabetic patients using PIO at Ramathibodi hospital were reviewed to compare outcomes and adverse effects between low and high doses of PIO. 38 patients who stabilized dose of PIO and agree to participate were recruited to collect 2 blood samples at 2 appropriated times and were analyzed their PIO concentrations, then, PK parameters were determined. The outcomes of glucose control and lipid control were not differences between low and high dose of PIO, but edema and HF events were significantly higher in high dose of PIO (P=0.010 and P=0.014, respectively). For PK parameters of PIO, elimination rate constant (ke) and clearance rate (CL) values of patients who were stabilized on high dose of PIO were significantly higher (P=0.022 and P=0.031, respectively) while elimination halflife (t1/2) was significantly shorter (P=0.007) than those who were stabilized on low dose of PIO. PK monitoring fo

Single measurement of intact parathyroid hormone after thyroidectomy can predict transient and permanent hypoparathyroidism: a prospective study

Objective: Immediate postoperative hypocalcemia is the most common complication of bilateral thyroidectomy. Although hypocalcemia is usually transient, it can be fatal. This study aimed to find a predictor of immediate postoperative hypocalcemia by using intact parathyroid hormone (PTH) level at 4 hours after thyroidectomy (iPTH4hr) compared with the decline in the percentage of intact PTH (%iPTH). We also followed the subjects for evaluation of permanent hypoparathyroidism. Methods: This was a prospective study of 65 patients (86.2% female, mean age: 43±15 years) who planned to undergo total or subtotal thyroidectomy. Preoperative and iPTH4hr were measured. Results: Thirty-nine patients (60%) were diagnosed with papillary thyroid carcinoma, while the rest were multinodular goiter (21.5%) and Graves' disease (7.7%). Significant immediate hypocalcemia was observed in 25 (38.5%) patients. Both iPTH4hr 72% could accurately predict significant immediate hypocalcemia. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for iPTH4hr were 92%, 87.5%, 82.1%, and 94.6%, respectively. The %iPTH decline was equal in accuracy, with sensitivity, specificity, PPV, and NPV of 84%, 90%, 84%, and 90%, respectively. At 6 months after surgery, 19 patients (29.2%) displayed permanent hypoparathyroidism. The iPTH4hr 72% could also predict permanent hypoparathyroidism, with sensitivity, specificity, PPV, and NPV of 100%, 80.4%, 67.9%, and 100%, and 94.7%, 84.8%, 72%, and 97.5%, respectively. Conclusions: Only a single measurement of iPTH4hr could be helpful in identifying patients at risk of significant immediate hypocalcemia in need prompt treatment, and subsequently facilitating early discharge of patients. Also, this parameter can precisely predict permanent hypoparathyroidism

A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia

Objective: To perform genetic linkage analysis in a family affected with ALS and frontotemporal dementia (FTD). Methods: The authors performed a genome-wide linkage analysis of a four-generation, 50-member Scandinavian family in which five individuals were diagnosed with ALS and nine with FTD. Linkage calculations assuming autosomal dominant inheritance of a single neurodegenerative disease manifesting as either ALS or FTD with age-dependent penetrance were performed. Further analyses for ALS alone and FTD alone were performed. A parametric logarithm of odds (lod) score of 2.0 or greater was required for further study of a potential locus and crossover (haplotype) analysis. Results: A new ALS-FTD locus was identified between markers D9s1870 and D9s1791 on human chromosome 9p21.3-p13.3. A maximum multipoint lod score of 3.00 was obtained between markers D9s1121 and D9s2154. Crossover analysis indicates this region covers approximately 21.8 cM, or 14Mb. Conclusions: A locus on chromosome 9p21.3-p13.3 is linked to ALS-FTD