of tigecycline is (4S,4aS,5aR,12aS)-9-[2-(tert-butylamino)acetamido]-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide. The empirical formula is CHNO and the molecular weight is 585.65.
The following represents the chemical structure of tigecycline:
TYGACIL is an orange lyophilized powder or cake. Each TYGACIL vial contains 50 mg tigecycline lyophilized powder for reconstitution for intravenous infusion and 100 mg of lactose monohydrate. The pH is adjusted with hydrochloric acid, and if necessary sodium hydroxide. The product does not contain preservatives.
Tigecycline is an antibacterial drug [see Clinical Pharmacology (12.4)].
The mean pharmacokinetic parameters of tigecycline after single and multiple intravenous doses based on pooled data from clinical pharmacology studies are summarized in Table 3. Intravenous infusions of tigecycline were administered over approximately 30 to 60 minutes.
Table 3. Mean (CV%) Pharmacokinetic Parameters of Tigecycline Single Dose Multiple Dosea
100 mg 50 mg every 12h
(N=224) (N=103)
a 100 mg initially, followed by 50 mg every 12 hours b 30-minute infusion c 60-minute infusion
Cmax (mcg/mL)b 1.45 (22%) 0.87 (27%)
Cmax (mcg/mL)c 0.90 (30%) 0.63 (15%)
AUC (mcg·h/mL) 5.19 (36%) - -
AUC0-24h (mcg·h/mL) - - 4.70 (36%)
Cmin (mcg/mL) - - 0.13 (59%)
t½ (h) 27.1 (53%) 42.4 (83%)
CL (L/h) 21.8 (40%) 23.8 (33%)
CLr (mL/min) 38.0 (82%) 51.0 (58%)
Vss (L) 568 (43%) 639 (48%)
The in vitro plasma protein binding of tigecycline ranges from approximately 71% to 89% at concentrations observed in clinical studies (0.1 to 1.0 mcg/mL). The steady-state volume of distribution of tigecycline averaged 500 to 700 L (7 to 9 L/kg), indicating tigecycline is extensively distributed beyond the plasma volume and into the tissues.
Following the administration of tigecycline 100 mg followed by 50 mg every 12 hours to 33 healthy volunteers, the tigecycline AUC (134 mcg·h/mL) in alveolar cells was approximately 78-fold higher than the AUC in the serum, and the AUC (2.28 mcg·h/mL) in epithelial lining fluid was approximately 32% higher than the AUC in serum. The AUC (1.61 mcg·h/mL) of tigecycline in skin blister fluid was approximately 26% lower than the AUC in the serum of 10 healthy subjects.
In a single-dose study, tigecycline 100 mg was administered to subjects prior to undergoing elective surgery or medical procedure for tissue extraction. Concentrations at 4 hours after tigecycline administration were higher in gallbladder (38-fold, n=6), lung (3.7-fold, n=5), and colon (2.3-fold, n=6), and lower in synovial fluid (0.58-fold, n=5), and bone (0.35-fold, n=6) relative to serum. The concentration of tigecycline in these tissues after multiple doses has not been studied.
Tigecycline is not extensively metabolized. In vitro studies with tigecycline using human liver microsomes, liver slices, and hepatocytes led to the formation of only trace amounts of metabolites. In healthy male volunteers receiving C-tigecycline, tigecycline was the primary C-labeled material recovered in urine and feces, but a glucuronide, an N- |
