Hypothyroid has still be a job in Thailand. Lack of pharmacokinetics information of levothyroxine in athyreotic patients for modify dosing. Therefore, the purpose of this survey was to look into the pharmacokinetic parametric quantities of 2 doses of levothyroxine ( 50 milligram and 100 milligram ) in such group of patients.

The 24 athyreotic patients were recruited and indiscriminately assigned to have 50 milligram or 100 milligram of levothyroxine. The pharmacokinetic parametric quantities ( Cmax, Tmax, AUC0-8, ke, T1/2 and Vd ) of FT4 and TSH were calculated by non-compartment theoretical account. The parametric quantities of 2 doses were compared. From the consequences found that, by supervising FT4, there were no statistically important difference ( p & A ; gt ; 0.05 ) of about all pharmacokinetic parametric quantities between 2 doses except Cmax which has important greater in 100 milligram of levothyroxine. While all pharmacokinetics parametric quantities of TSH were non statistically important difference.

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The usage of non-compartment theoretical account seems appropriate for computation of pharmacokinetic parametric quantities of FT4 ( R2 = 0.81 ) while it has hapless prognostic capacity in footings of TSH ( R2 = 0.24 ) . In decision, disposal of 50 milligrams and 100 milligram of leveothyroxine to athyreotic patients have similar pharmacokinetic in term of FT4 ( non-significant different in Tmax, AUC ) and TSH. Further survey of these parametric quantities in more topics is needed.

Cardinal word: Pharmacokineticss, Athyreotic patients, Levothyroxine


Hypothyroid is the status that largely found in athyreotic patients. The incidence of low free T4 ( FT4 ) and high Thyroid Stimulating Hormone ( TSH ) is about 0.3 % while the incidence of low thyroid endocrine is found to 4.3 % [ 1-3 ] The general intervention of hypothyroid should bit by bit modified drug dosing. American Association of Clinical Endocrinologists recommended Levothyroxine ( L-T4 ) 1.

6 mcg/kg/day by Begin with 12.5 mcg/day and so increase dosage bit by bit depends on age, weight, cardiovascular position and continuance of hypothyroid [ 4, 5 ]In Thailand, the endocrinal specializer recommended high dose unwritten levothyroxine 1000 & A ; Acirc ; µg for individual dosage. Presently there have non been studied of efficaciousness and side effects of high doses regimen.However, there are several surveies in high doses of levothyroxin in patients with hypothyroid [ 6, 7 ] , the survey found that myxoedema coma or myxoedema intestinal obstruction, Levothyroxine oral path has variable soaking up but patients had better response after disposal. Intravenous levothyroxine can do higher degree of thyroid endocrine. However, it can non reason that, which appropriate dosage should be administered in terrible hypothyroidism.

Vicky Blakesley et Al [ 8 ] reported Bioequivalence of Levothyroxine unwritten 400, 450 and 600 milligram in healthy voluntary and measured thyroid endocrine to find Cmax ( maximal serum concentration ) , clip to Cmax, and AUC ( country under the serum concentration-time curve ) and suggested that the bioequivalence survey of levothyroxine should utilize endogenoud T4 in the computation and the serious inauspicious effects were non found in high dose levothyroxine. In Thailand, there is deficiency of pharmacokinetic information of levothyroxine pharmacokinetics in hypothyroid patients. Therefore, this survey aimed to look into the pharmacokinetic parametric quantities of 2 doses levothyroxine in such patients.

Materials and methods


Twenty four primary hypothyroidism patients with implicit in well-differentiated thyroid malignant neoplastic disease were recruited. Patients had Entire or Near-total thyroidectomy and halt levothyroxine for 6 hebdomads and had 131I radiation therapy which is available as standard intervention.Inclusion standardsMales or females whose ages between 15-60 old ages oldTSH & A ; gt ; 30mIU/mLNo underlying diseases such as Cardiovascular diseases, Liver inadequacy ( AST and/or ALT & A ; gt ; 3 times UL ) , nephritic inadequacy ( Scr & A ; gt ; 1.5 mg/dL )No having other drugs that consequence levothyroxine soaking up such as Ca incorporating drugs, antiepileptics, estrogens, and proton pump inhibitors or H2 blockers.Exclusion standardsPatients were excluded if theywere hapless conformity with drug regimenswere gestation or lactationhad hypersensitivity or intolerate to thyroxinehad infective or liver diseaseswere considered by physician as inappropriate to be included in this survey.

Drug disposal

Patients were administered levothyroxine 50 milligram ( 50mg ) 1 tablets or Levothyroxine 100 milligram ( 50mg 2 tablets ) individual dosage.

Pharmacokinetic survey

Pharmacokinetic analysisLevothyroxine plasma concentrations were analyzed as a map of clip and the undermentioned pharmacokinetic parametric quantities were obtained for each topic ; the maximal plasma concentration ( Cmax ) , Area under the concentration versus clip curve for 8 hours ( AUC0-8 ) , Elimination rate constatnt ( ke ) , and volume of distribution ( Vd ) . All pharmacokinetic parametric quantities of free T4 ( FT4 ) and Thyroid Stimulation endocrine ( TSH ) were assessed by Win-nonlin professional package ( version1, Pharsight corporation, Pato Alta, California ) and non-compartment methods was used.

Datas analysis

Student t-test statistic was used to prove the different of pharmacokinetic parametric quantities between 2 groups of different regimens. The statistical important difference was considered when p value was less than 0.05.


The pharmacokinetic parametric quantities that found in 24 hypothyroid topics was presented in Table 1 and Table 2 severallyTable 1 Pharmacokinetics parametric quantities of FT4 in 24 hypothyroid topicsAverage R2 = 0.

81Table 2 Pharmacokinetics parametric quantities of TSH in 24 hypothyroid topicsAverage R2 = 0.24


Harmonizing to the consequences, the pharmacokinetic parametric quantities of levothyroxine 50 milligram and 100 milligram which step by proctor FT4 have non important difference except peak concentration ( Cmax ) is higher in levothyroxine 100 milligram, while all pharmacokinetic parametric quantities in footings of TSH were non important difference. It seems that may be the pharmacokinetic of levothyroxine may hold non-linear behaviour.When comparing of these parametric quantities with old survey found that, the tmax and mean half life were similar to this survey. [ 9-11 ] The much fluctuations is Cmax and AUC when comparison to old surveies since due to the hypothyroid position of patients in this survey which may had lower T4 base line and 50-100 milligram individual dosage can non do FT4 make for normal scope and it implied that non-compartmental method can be used in computation of pharmacokinetic parametric quantities of LT4 with good Roentgen 2 ( mean = 0.8 ) , while is non appropriate usage for TSH because R 2 is rather low ( mean =0.2 ) .

More over the sensitiveness of TSH is less than FT4.This survey leads to carry set uping the usage of pharmacokinetic theoretical account for supervising FT4 in athreotic patients which is utile in levothyroxine dose accommodation.However, this survey had some restrictions, because of little figure of topics, the pharmacokinetics parametric quantities may be non generalized for every patient, farther survey with more figure of topics are needed. The 2nd point is there is no perennial survey for application of this theoretical account to another group of patients for turn outing about the truth of the theoretical account.

Using this theoretical account for levothyroxine dose accommodation in another group of athyreotic patients for mensurating the truth may assist to turn out about generalisation of this proposed theoretical account.In decision, disposal of levothyroxine ( 50 milligram ) and levothyroxine ( 100 milligram ) have similar pharmacokinetic in term of FT4 ( non-significant different in Tmax, AUC ) and TSH. Further survey of these parametric quantities in more topics is needed.