JAC Advance Access originally published online on September 29, 2006
Journal of Antimicrobial Chemotherapy 2006 58(6):1221-1229; doi:10.1093/jac/dkl403
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Serum, tissue and body fluid concentrations of tigecycline after a single 100 mg dose
1 Department of Pharmacy Practice, College of Pharmacy University of Illinois at Chicago, Chicago, IL 60612, USA 2 College of Medicine The University of Arizona, Phoenix, AZ 85012, USA 3 Pulmonary Associates PA, 1112 E McDowell Road, Phoenix, AZ 85006, USA 4 IIT Research Institute Life Sciences Group, 10 West 35th Street, Chicago, IL 60616, USA 5 Clinical Research Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
Received 22 April 2006; returned 16 June 2006; revised 13 August 2006; accepted 9 September 2006
*Corresponding author. Tel: +1-312-996-3341; Fax: +1-312-413-1797; E-mail: kar{at}uic.edu
Objectives: The purpose of this study was to determine the tissue and corresponding serum concentration of tigecycline at selected time points in gall bladder, bile, colon, bone, synovial fluid (SF), lung and CSF in subjects undergoing surgical or medical procedures.
Methods: One hundred and four adult subjects (aged 24–83 years; 64 women, 40 men) received a single intravenous (iv) dose of tigecycline (100 mg infused over 30 min). Subjects were randomly assigned to one of four collection times at 4, 8, 12 and 24 h after the start of the infusion. For CSF, samples were collected at approximately 1.5 and 24 h after the start of the infusion. All subjects had serum samples collected before the administration of tigecycline, at the end of the infusion and at the time corresponding to tissue or body fluid collection. Drug concentrations in serum, tissues and body fluids were determined by LC/MS/MS. The area under the mean concentration–time curve from 0 to 24 h (AUC0–24) was determined for the comparison of systemic exposure between tissue or body fluid to serum.
Results: The mean serum concentrations of tigecycline were similar to those previously published. Tissue penetration, expressed as the ratio of AUC0–24 in tissue or body fluid to serum, was 537 for bile, 23 for gall bladder, 2.6 for colon, 2.0 for lung, 0.41 for bone, 0.31 for SF and 0.11 for CSF.
Conclusions: A single 100 mg dose of intravenous tigecycline produced considerably higher tissue/fluid concentrations in bile, gall bladder, colon and lung compared with simultaneous serum concentrations. On average, the systemic exposure of tigecycline in bone, SF and CSF ranged from 11% to 41% of serum concentrations. The results in bone are inconsistent with previous radiolabelled studies in animals and it is unclear if tight binding to bone (versus low bone uptake) or poor extraction of tigecycline for LC/MS/MS detection or both may have contributed to the differences we observed in humans.
Keywords: pharmacokinetics , pharmacodynamics , tissue penetration , glycylcyclines
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