Three-compartmental analysis of effects of D-propranolol on thyroid hormone kinetics

Abstract

Tracer thyroxine (T4), 3.3',5-triiodothyronine (T3), and 3,3',5'-triiodothyronine (rT3) kinetic studies were performed in normal T4 substituted subjects before and during oral D-propranolol treatment to determine whether changes in thyroid hormone metabolism in a propranolol-induced low-T3 syndrome result from inhibition of 5'-deiodination or inhibition of transport of iodothyronines into tissues. Data were analyzed according to a three-compartmental model of distribution and metabolism. T4 plasma appearance rate decreased by 16% (P less than 0.01), reflecting a decreased intestinal absorption of orally administered T4 during propranolol. Serum T4 and free T4 levels increased significantly by 14%, whereas T4 metabolic clearance rate (MCR) was lowered by 26% (P less than 0.001). No changes were observed in size of the three T4 compartments or in fractional and mass transfer rates of T4 from plasma to the rapidly (REP) and slowly (SEP) equilibrating pools. Serum T3, free T3, T3 plasma pool, T3 mass transfer rate to REP and SEP, and the T3 pool masses were all significantly decreased during propranolol to a similar extent as the T3 plasma production rate (PR). T3 MCR decreased by 14% (P less than 0.05). Serum total and free rT3 increased, whereas the rT3 MCR was substantially lowered during propranolol (P less than 0.001). The rT3 plasma pool, rT3 REP and SEP, and the mass transfer rates to REP and SEP increased, whereas no alterations were observed in rT3 PR and fractional transfer rates of rT3 to REP and SEP.(ABSTRACT TRUNCATED AT 250 WORDS)

The sick euthyroid syndrome: changes in thyroid hormone serum parameters and hormone metabolism

“…Eber et a/. (1990) showed that this effect is due to the presence of d-propranolol in the mixture, and is probably caused by the inhibition of type I deiodinase in the liver (Van der Heyden et al, 1988). This enzyme inhibition by propranolol was also shown in rats (Hcyrna rt ul., 1980).…”

“…uT3 kinetics. rT3 serum concentrations are increased and metabolic clearance rates are decreased in patients with NTI (Chopra, 1976;Suda et al, 1978;Faber el al., 1981;Kaptein e f al., 1982b;Van der Heyden et al, 1988), but both arc gcnerally normal in those with renal disease (Kaptein et al, 1983;Faber et al, 1983). Production rates of rT3 are normal in both groups of patients.…”

The hidden, nonexchangeable pool of 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine in man: does it exist?

“…Two previous studies provide data from simulta¬ neous turnover studies of both T4, T.f and rT3 (Suda et at. 1978;van der Heijden et al 1988). In contrast to the present investigation, these studies were performed on normal subjects receiving 0.2 mg L-T4 daily.…”

Nanoclay-Based Composite Films for Transdermal Drug Delivery: Development, Characterization, and in silico Modeling and Simulation

“…Contemplating the oral administration of 80 mg propranolol and to simulate the systemic disposition into individuals with an average weight of 75 kg as a comparison parameter, the three-compartmental model was selected with the help of the PKPlus® module. 69 Different formulations, pharmacokinetics, and physiological parameters are illustrated in Table 2 . The mean pharmacokinetic parametric values ( Table 7 ) for F6 were calculated as 32.113 ng/mL ( C max ), 16.58 h ( T max ), 942.34 ng/mL×h ( AUC t ) and 1102.9 ng/mL×h ( AUC inf ).…”