No data are available on whether tigecycline can cross the blood-brain barrier in humans.

In clinical pharmacology studies using the therapeutic dosage regimen of 100 mg followed by 50 mg q12h, serum tigecycline steady-state Cmax was 866±233 ng/ml for 30-minute infusions and 634±97 ng/ml for 60-minute infusions. The steady-state AUC0-12h was 2349±850 ng•h/ml.

Biotransformation

On average, it is estimated that less than 20 % of tigecycline is metabolised before excretion. In healthy male volunteers, following the administration of 14C-tigecycline, unchanged tigecycline was the primary 14C-labelled material recovered in urine and faeces, but a glucuronide, an N-acetyl metabolite and a tigecycline epimer were also present.

In vitro studies in human liver microsomes indicate that tigecycline does not inhibit metabolism mediated by any of the following 6 cytochrome P450 (CYP) isoforms: 1A2, 2C8, 2C9, 2C19, 2D6, and 3A4 by competitive inhibition. In addition, tigecycline did not show NADPH-dependency in the inhibition of CYP2C9, CYP2C19, CYP2D6 and CYP3A, suggesting the absence of mechanism-based inhibition of these CYP enzymes.
Elimination

The recovery of the total radioactivity in faeces and urine following administration of 14C-tigecycline indicates that 59 % of the dose is eliminated by biliary/faecal excretion, and 33 % is excreted in urine. Overall, the primary route of elimination for tigecycline is biliary excretion of unchanged tigecycline. Glucuronidation and renal excretion of unchanged tigecycline are secondary routes.

The total clearance of tigecycline is 24 L/h after intravenous infusion. Renal clearance is approximately 13 % of total clearance. Tigecycline shows a polyexponential elimination from serum with a mean terminal elimination half-life after multiple doses of 42 hours although high interindividual variability exists.

Special populations

Hepatic Insufficiency

The single-dose pharmacokinetic disposition of tigecycline was not altered in patients with mild hepatic impairment. However, systemic clearance of tigecycline was reduced by 25 % and 55 % and the half-life of tigecycline was prolonged by 23 % and 43 % in patients with moderate or severe hepatic impairment (Child Pugh B and C), respectively (see section 4.2).
Renal Insufficiency

The single dose pharmacokinetic disposition of tigecycline was not altered in patients with renal insufficiency (creatinine clearance <30 ml/min, n=6). In severe renal impairment, AUC was 30 % higher than in subjects with normal renal function (see section 4.2).

Elderly Patients

No overall differences in pharmacokinetics were observed between healthy elderly subjects and younger subjects (see section 4.2).

Paediatric Population

The safety and efficacy of tigecycline in the paediatric population 8 to <18 years of age have not been established.

Tigecycline pharmacokinetics was investigated in two studies. The first study enrolled children aged 8-16 years (n=24) who received single doses of tigecycline (0.5, 1, or 2 mg/kg, with no dose limitation) administered intravenously over 30 minutes. The second study was performed in children aged 8 to 11 years (n=47) who received multiple doses of tigecycline (0.75, 1, or 1.25 mg/kg up to a maximum dose of 50 mg) every 12 hours administered intravenously over 30 minutes. No loading dose was admini