Rifabutin (Blood)

Diagnostic Use

Rifabutin is a second line treatment for TB or non-TB mycobacterial infections. As it is less potent than Rifampicin in inducing hepatic drug clearance, it can be used in situations with potentially complex drug-drug interactions e.g. patients also on AIDS treatment or seizure control medications. On the other hand, as Rifabutin is metabolised by hepatic microsomal enzymes and intestinal CYP3A4 and its active metabolite 25-O-desacetyl by hepatic CYP3A4, they can be influenced by enzyme induction or inhibitory effects by e.g. Efavirenz and Clarithromycin/Diltiazem/Ketoconazole respectively. Coupled with its known concentration dependent toxicities like anterior uveitis and neutropenia and its overall low oral bioavailability, selected patients would benefit from Rifabutin therapeutic drug monitoring to achieve better anti-microbial efficacy as well as to avoid toxicities.

Many other commonly prescribed drugs metabolised by this cytochrome P450 enzyme complex and may also affect metabolism, visit:

Drug Metabolism – The Importance of Cytochrome P450 3A4

In a patient on Rifabutin 300mg once daily dose, the steady state peak concentration is usually reached by 2-4 hours post-dose. We recommend collection of plasma samples before the next dose as well as at 3 hours and 4 hours post-dose. In patients suspected of having delayed absorption, an additional blood collection at 7 hours post-dose may help in the evaluation. Its pre-dose level is usually <100 ug/L. The recommended plasma peak concentration is between 450-900 ug/L.

Interpretation

Normally   plasma concentration of the active 25-O-desacetyl metabolite (may be 25-50% as potent as Rifabutin) is relatively minor, at about 5-10% of the parent compound. However its clearance can be disproportionally impaired by strong CYP3A4 inhibitors e.g. some protease inhibitors like Ritonavir or by renal impairment (creatinine clearance <50ml/min) causing increase in the metabolite’s level , consequently contributes towards increase risk of toxicity.   Literature suggests increased risk of neutropenia and anterior uveitis when the sum of Rifabutin and 25-O-desacetylRifabutin is more than 1000 ug/L.

Note that LabPlus:  current method only reports   Rifabutin concentration. It does NOT include the 25-O-desacetyl active metabolite level.

Reference Intervals

The therapeutic range quoted relates to the peak concentration.

Therapeutic – Units: ug/L