Pharmacokinetic Study of Minocycline in Patients With Pulmonary Nontuberculous Mycobacterial Disease

Inclusion Criteria:

• 2020 guideline (ATS/ERS/ESCMID/IDSA) diagnostic criteria for nontuberculousmycobacterial pulmonary disease are met, i.e. the patient is symptomatic, hasnodules, bronchiectasis or fibro-cavitary lesions seen on (HR)CT scan of the lungsand ≥2 positive sputum cultures or one positive bronchoalveolar lavage culture ofthe same M. avium complex species.

• At least one of the positive cultures must be done in the last 4 months beforeinclusion.

• The subject is eligible to start the guideline-recommended rifampicin-based regimenaccording to the treating physician.

• Age ≥ 18 years.

• Signed and dated patient informed consent.

Exclusion Criteria:

• A relevant medical history or current condition that might interfere with drugabsorption, distribution, metabolism or excretion (i.e. chronic gastro-intestinaldisease, renal or hepatic disease).

• Diagnosed with cystic fibrosis (as this may affect the pharmacokinetics of drugs).

• Pregnant or breastfeeding (contra-indications for minocycline) or inadequatecontraceptive measures (in view of the administration of rifampicin which interactswith oral contraceptive drugs, adequate contraceptive measures are abstinence fromsexual activities and barrier methods).

• Use of drugs that cause a relevant drug interaction with minocycline, i.e. oralmagnesium, , bismuth, aluminium, calcium, zinc or iron containing formulations,antacid drugs and drugs besides rifampicin that are strong inducers of metabolicenzymes, including barbiturates, carbamazepin and phenytoin (as judged by theinvestigators).

• ALAT > 3 times the upper limit of normal (normal <45 U/l).

• ASAT > 3 times the upper limit of normal (normal <35 U/l).

• An abnormal serum creatinine level (defined as a level that is higher than the upperlimit of normal, i.e. >110 umol/l).

• Active alcohol abuse.

• Hypersensitivity to minocycline or to other tetracycline antibiotics.