Levothyroxine pharmacokinetics

Loss of efficacy relates to the pharmacokinetic properties of the drugs. With some short t/f drugs there is a simple issue of a transient drop in plasma concentration below a defined therapeutic level. But with others there may be complex issues such as recovery of negative feedback homoeostatic mechanisms, e.g. adrenocortical steroids. Therajjeutic effect may not decline in parallel with plasma concentration. With some drugs a single missed dose may be important, e.g. oral contraceptives, with others (long tj ) several doses may be omitted before there is any serious decline in efficacy, e.g. thyroxine (levothyroxine). 

Table 34.2. Some Properties and Pharmacokinetics for Levothyroxine and Liothyroninea ...

In a pharmacokinetic study, grapefruit juice had little effect on the absorption of levothyroxine, suggesting a clinically relevant interaction is unlikely. However, there is one case of unexplained hypothyroidism in a patient taking levothyroxine, which resolved when grapefruit juice consumption was reduced. 

In one study, patients who had been taking levothyroxine and omeprazole for a least 6 months required a modest 37% increase in the median levothyroxine dose required to suppress TSH levels to those seen before starting omeprazole. Conversely, in a pharmacokinetic study, pantoprazole did not alter the absorption of a single dose of levothyroxine. 

An interaction between levothyroxine and proton pump inhibitors is not established. The pharmacokinetic study witii pantoprazole did not reveal a change in levothyroxine absorption, whereas the study in patients who had been taking omeprazole for 6 months suggested that patients may need a modest increase in levothyroxine dose. Bear in mind the possibility of an interaction if a patient starting a proton pump inhibitor shows signs of reduced levothyroxine efficacy. Any interaction may take several months to develop. Further study is needed. 

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