Summary of Pharmacokinetics and Tissue Distribution of a Broad-Spectrum Fluoroquinolone, JNJ-Q2.
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.
Furiex Pharmaceuticals Inc, Morrisville, NC, USAPulmonary Associates, Phoenix, AZ, USAPPD Inc, Austin, TX, USAPPD Inc, Richmond, VA, USA.
J Michael
JM
Davenport
Furiex Pharmaceuticals Inc, Morrisville, NC, USAPulmonary Associates, Phoenix, AZ, USAPPD Inc, Austin, TX, USAPPD Inc, Richmond, VA, USA.
Paul
P
Covington
Furiex Pharmaceuticals Inc, Morrisville, NC, USAPulmonary Associates, Phoenix, AZ, USAPPD Inc, Austin, TX, USAPPD Inc, Richmond, VA, USA.
Mark
M
Gotfried
Furiex Pharmaceuticals Inc, Morrisville, NC, USAPulmonary Associates, Phoenix, AZ, USAPPD Inc, Austin, TX, USAPPD Inc, Richmond, VA, USA.
Matthew
M
Medlock
Furiex Pharmaceuticals Inc, Morrisville, NC, USAPulmonary Associates, Phoenix, AZ, USAPPD Inc, Austin, TX, USAPPD Inc, Richmond, VA, USA.
Prapoch
P
Watanalumlerd
Furiex Pharmaceuticals Inc, Morrisville, NC, USAPulmonary Associates, Phoenix, AZ, USAPPD Inc, Austin, TX, USAPPD Inc, Richmond, VA, USA.
Gail
G
McIntyre
Furiex Pharmaceuticals Inc, Morrisville, NC, USAPulmonary Associates, Phoenix, AZ, USAPPD Inc, Austin, TX, USAPPD Inc, Richmond, VA, USA.
Lisa
L
Turner
Furiex Pharmaceuticals Inc, Morrisville, NC, USAPulmonary Associates, Phoenix, AZ, USAPPD Inc, Austin, TX, USAPPD Inc, Richmond, VA, USA.
June
J
Almenoff
fluoroquinolone; lung penetration; pharmacokinetics