Please contact the laboratory in advance if levels are required.
Rifabutin is prone to post-collection degradation.
Protect collection tube from light.
Mark as urgent and separate sample within 6 hours from collection and wrap in tin foil.
We recommend collection of plasma samples before the next dose as well as at 3 hours and 4 hours post-dose
If test is to be delayed, the separated serum should be stored frozen and transport on ice.
The therapeutic range quoted relates to the peak concentration.
Uncertainty of measurement: 16%
| Age Range | Either Sex |
|---|---|
| All | 450 - 900 |
High performance liquid chromatography (HPLC)
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:
https://www.medsafe.govt.nz/profs/puarticles/march2014drugmetabolismcytochromep4503a4.htm
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.
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.
References:
Alsultan A, Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis: an update. Drugs 2014; 74:839-854
Crabol Y, Catherinot E et al. Rifabutin: where do we stand in 2016 ? J Antimicrob Chemother 2016; 71:1759-1771
Emails to chemicalpathologist@adhb.govt.nz will receive priority attention from the on-call chemical pathologist.
If the query concerns a specific patient please include the NHI number in your email.
If email is not a suitable option, please contact the on-call chemical pathologist via Lablink (Auckland City Hospital ext. 22000 or 09-3078995).
Individual chemical pathologists may be contacted but will not be available at all times.
After-hours : contact Lablink (Auckland City Hospital ext. 22000 or 09-3078995) or hospital operator for on duty staff after hours.
Dr Samarina Musaad (Clinical Lead) : SamarinaM@adhb.govt.nz ext. 22402
Dr Cam Kyle: CampbellK@adhb.govt.nz ext 22052
Dr Weldon Chiu: WeldonC@adhb.govt.nz ext. 23427
Dr Campbell Heron: CHeron@adhb.govt.nz ext. 23427
Dr Sakunthala Jayasinghe: Sakunthala@adhb.govt.nz ext. 23427