Antimycobacterial treatment of M. avium complex pulmonary disease (MAC-PD) has suboptimal cure rates and is challenging due to frequent adverse drug reactions and drug-drug interactions. Hence, there is an urgent need for improved treatment regimens with effective and tolerable antibiotics. Minocycline is a well-tolerated, orally administered tetracycline-type antibiotic with in vitro activity against MAC, but pharmacokinetic data in the target population is lacking. Moreover, rifampicin, a strong inducer of cytochrome P450 enzymes involved in drug metabolism and of various drug transporters, is part of the current first-line MAC-PD treatment regimen and has a substantial interaction with doxycycline, a related tetracycline. Pharmacokinetic data in the target population will allow us to propose an appropriate dose of minocycline when co-administered with or without rifampicin Mino-PK is an open label, one-arm, two-period, fixed-order pharmacokinetic study that will assess exposure to minocycline in MAC-PD patients with and without concurrent use of rifampicin. Subjects will receive two 5-day dosing periods of minocycline; the first without and second with concurrent use of rifampicin. Minocycline plasma concentrations will be determined after both dosing periods.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Patients with M. avium complex pulmonary disease will receive 200 mg of minocycline for 5 days before starting rifampicin and after 1 month (±1 week) of receiving rifampicin. Antimycobacterial drugs other than rifampicin can be started prior to or simultaneous with the first minocycline dosing period as part of standard care. At day 5 of both minocycline dosing periods, blood will be sampled for minocycline plasma concentration measurements at T = 0, 1, 2, 3, 4, 6, 8 and 24 hours.
Radboud University Medical Center
Nijmegen, Gelderland, Netherlands
Pharmacokinetic parameters of minocycline in MAC-PD patients without concurrent use of rifampicin.
The area under the curve (AUC0-24h)
Time frame: Day 5 of the first minocycline dosing period
Pharmacokinetic parameters of minocycline in MAC-PD patients without concurrent use of rifampicin.
The peak plasma concentration (Cmax)
Time frame: Day 5 of the first minocycline dosing period
Pharmacokinetic parameters of minocycline in MAC-PD patients without concurrent use of rifampicin.
The plasma trough concentration (Cmin)
Time frame: Day 5 of the first minocycline dosing period
Pharmacokinetic parameters of minocycline in MAC-PD patients with concurrent use of rifampicin.
The area under the curve (AUC0-24h)
Time frame: Day 5 of the second minocycline dosing period
Pharmacokinetic parameters of minocycline in MAC-PD patients with concurrent use of rifampicin.
The peak plasma concentration (Cmax)
Time frame: Day 5 of the second minocycline dosing period
Pharmacokinetic parameters of minocycline in MAC-PD patients with concurrent use of rifampicin.
The plasma trough concentration (Cmin)
Time frame: Day 5 of the second minocycline dosing period
Pharmacokinetic parameters of rifampicin in MAC-PD patients
The peak plasma concentration (Cmax)
Time frame: Day 5 of the second minocycline dosing period
Adverse Events
The number of (participants with) adverse events will be measured. Adverse events will be graded according to the 'Common Terminology Criteria for Adverse Events' (CTCAE)
Time frame: Through study completion, an average of 6 weeks
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