Pharmacokinetics of rifampicin in Mexican patients with tuberculosis and healthy volunteers.
OBJECTIVE
The aim of this study was to compare the pharmacokinetics (PK) of rifampicin (RIF) between healthy volunteers and patients with tuberculosis (TB).


METHODS
RIF was administered as a single 600-mg dose to 24 healthy volunteers and 24 TB patients, followed by serial blood sampling. Plasma concentrations were analysed using a chromatographic method, and the PK parameters were estimated using WinNonlin software.


RESULTS
Peak plasma concentration ranged from 6.4 to 19.9 mg/l, which was subtherapeutic for 15% of the study participants in both groups, mostly in men (71.4%). The mean area under the concentration-time curve (AUC0-24h ) did not show differences between these groups (P > 0.05). The absorption rate was slower in TB patients and the volume of distribution normalized by total body weight (Vd/kg) was greater than healthy volunteers (P < 0.05). A greater Vd and clearance were found in male subjects. The lag time (tlag) and the time before reach Cmax (Tmax) were longer for female TB patients (P < 0.05).


CONCLUSIONS
The main differences in PK parameters of RIF between Mexican TB patients and healthy volunteers were demonstrated in absorption and distribution processes. In addition, differences in PK parameters observed by sex should be considered for further dosing recommendations.
Facultad de Ciencias Químicas, UASLP, San Luis Potosí, SLP, México.
Susanna E
SE
Medellín-Garibay
Rosa Del Carmen
Rdel C
Milán-Segovia
Martín
M
Magaña-Aquino
Diana Patricia
DP
Portales-Pérez
Silvia
S
Romano-Moreno
D000328:Adult; D000904:Antibiotics, Antitubercular / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008800:Mexico; D008875:Middle Aged; D012016:Reference Values; D012293:Rifampin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012737:Sex Factors; D014376:Tuberculosis / Q000188:drug therapy*; D055815:Young Adult
D000904:Antibiotics, Antitubercular; D012293:Rifampin
HPLC; pharmacokinetics; rifampicin; tuberculosis