Summary of Pharmacokinetics and Tissue Distribution of a Broad‐Spectrum Fluoroquinolone, JNJ‐Q2

Abstract

This article summarizes key pharmacokinetic properties of JNJ-Q2, a broad-spectrum fluoroquinolone, being developed for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Two randomized placebo-controlled studies and one open-label study are presented: single and multiple ascending-dose studies evaluating intravenous (IV) and oral pharmacokinetics, absolute bioavailability accumulation, and lung penetration. Fifty-seven participants received JNJ-Q2, which was safe and well tolerated. The half-life was 13 to 20 hours, clearance (CLtot ) was 4.41 to 6.22 L/h, volume of distribution (Vd ) was 86 to 148 L, renal clearance (CLren ) was 0.58 L/h, and the fraction excreted in urine (%Fe) was 12%. Accumulation ratio was 1.63, and absolute bioavailability was 0.65. The lung penetration study demonstrated substantial concentration of JNJ-Q2 in epithelial lining fluid and alveolar macrophages with ratios to free plasma of 50.6 and 156.9, respectively, at 6 hours postdose. JNJ-Q2 doses under consideration for future clinical trials are 150 mg for IV and 250-mg tablets for oral administration.

Advances in the medical management of skin and soft tissue infections

“…These adverse effects were similar with oral administration. 94 was cure rate seven to 14 days after the completion of therapy, and ceftobiprole was found to be non-inferior to vancomycin. The second study was a multicenter, randomized, double blind trial in adults with cSSSIs comparing a different dosing strategy of ceftobiprole, 500 mg intravenously every eight hours infused over two hours, with vancomycin 1000 mg intravenously every 12 hours plus ceftazidime 1000 mg intravenously every eight hours.…”

“…94 In travenous doses of up to 150 mg twice daily have been tolerated, with gastrointestinal adverse effects, headache, and contact dermatitis being the most prominent. These adverse effects were similar with oral administration.…”

Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms

“…Multiple in vitro studies also found that avarofloxacin has a relatively lower risk for developing resistant mechanisms in S. pneumoniae and S. aureus than other fluoroquinolones [86,174,175]. In terms of pharmacokinetic parameters, avarofloxacin has an estimated absolute oral bioavailability of 65%, and is extensively distributed into ELF and AM [176]. However, only 12% of active drug is excreted by urine, which suggests that its clinical utility for treating urinary tract infections may be limited [171,176].…”

“…In terms of pharmacokinetic parameters, avarofloxacin has an estimated absolute oral bioavailability of 65%, and is extensively distributed into ELF and AM [176]. However, only 12% of active drug is excreted by urine, which suggests that its clinical utility for treating urinary tract infections may be limited [171,176]. The half-life of avarofloxacin is 13 to 20 h and is renally cleared at a rate of 0.58 L/h [176].…”

Renaissance of antibiotics against difficult infections: Focus on oritavancin and new ketolides and quinolones

“…Pharmacokinetic data from phase I (Table III) reported a C max of approx. 2 mg/L, and AUC of 28 mg.h/L and a half-life of approximately 14 h for an oral dose of 250 mg, with ELF/plasma and alveolar macrophages ratios ranging, respectively, between 17 and 64, and 74 and 157 (109). A first published report of a phase II study showed comparable cure rates for avarofloxacin (150 mg intravenously twice daily followed by 250 mg orally twice daily) and moxifloxacin (400 mg once daily, intravenously or orally) for the treatment of community-acquired infection (110).…”