Insights into the pharmacokinetic properties of antitubercular drugs

ABSTRACT

Introduction: The furiously advancing cases of multidrug-resistant tuberculosis (TB) along with the recent emergence of total drug resistant TB and TB-AIDS comorbidity present an increased threat to global public health. Knowledge of pharmacokinetic properties helps in selecting an appropriate anti-TB dosage regimen to achieve optimal results in patients.

Areas covered: This article provides a brief compilation of the information available regarding published pharmacokinetic data for anti-TB drugs and may act as a single window for investigators/medical practitioners in this field. The information regarding absorption, tissue distribution, elimination and pharmacokinetic interactions of the first- and second-line anti-TB drugs and candidate drugs under clinical trials is discussed.

Expert opinion: Pharmacokinetic properties such as poor absorption, too short biological half-life, extensive first-pass metabolism, drug-food and drug-drug related interactions are not attractive for prospective anti-TB drugs and significantly contribute to treatment failure and further resistance. The long duration, monotonous and multidrug treatment plan leads to poor patient compliance and resulted in a greater occurrence of anti-TB drug resistance worldwide. Few new agents, which are in development phase, are considering the aspect of shortening duration of the treatment regimen and provide a boost in therapy that is sorely needed.

KEYWORDS:

• Anti-TB
• absorption
• distribution
• excretion
• metabolism

Article highlights

• A thorough evaluation of the pharmacokinetic properties of all the existing anti-TB drugs will aid in understanding and grading their therapeutic performance in patients.

• Most anti-TB drug candidates get readily and almost completely absorbed from the gastrointestinal tract after oral administration and are widely distributed into body fluids and tissues but higher residence time in infected tissue is desirable.

• The lack of consideration of the pharmacokinetic properties of anti-TB drugs during the selection of regimen contributes to treatment failures and further resistance in patients.

• A multidrug therapy is being followed in the treatment of TB, so the risk of drug-drug interactions is very high, especially in patients co-infected with HIV.

• High dose rifampicin or moxifloxacin owns the potential to shorten the treatment duration.

• A major pharmacogenetic concern arises due to genetic variation in the activity of N-acetyltransferase enzyme responsible for the acetylation of isoniazid.

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Declaration of interests

The authors M Shukla and S Jaiswal were supported by the Council of Scientific and Industrial Research (CSIR) with research fellowships for this CDRI communication (9220). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed