Pharmacokinetics and human tissue penetration of flurithromycin

Abstract

The relationship between concentrations in serum and levels in tissue of flurithromycin, a new fluorinated macrolide, was determined in patients undergoing maxillofacial surgery and thoracotomy. All patients received 500 mg of flurithromycin orally every 8 h. Drug levels in serum, bone, soft tissue, lung, and pericardial fluid were determined microbiologically. The total amount of antibiotic per gram of tissue was calculated on the basis of the concentration in the supernatant of the homogenate. From the parallel course between free concentrations in serum and calculated contents in interstitial fluid tissue, it was concluded that the tissues examined were easily accessible by flurithromycin; penetration values measured by the ratio of areas under the curve were 8.3 for lung, 3.6 for bone, and 0.8 for soft tissue. The results of the pharmacokinetic study suggest that accumulation of the drug during repetitive multiple doses is predictable. Mean residence times were 10.2 and 8.3 h in groups 1 and 2, respectively. For bacteriostatic drugs such as macrolides, not only very high but also prolonged concentrations in tissue lead to favorable therapeutic result.

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

“…This value can be supported by the large volume of distribution [93]. Regarding antibacterial agents, pefloxacin (a quinolone drug) also penetrates cardiac muscle (Kp = 2.8) [89].…”

Antimicrobial Therapy for the Elderly Patient

“…However, since renal excretion is not a major mechanism for erythromycin clearance, it may be assumed that in relatively healthy elderly persons the drug pharmacokinetics is most likely unchanged. In a pharmacokinetic and tissue penetration study of flurithromycin, a group of young patients (20 to 31 years) undergoing maxillofacial surgery and a group of older patients (56 to 68 years) undergoing thoracotomy were investigated 252 . There appeared to be no significant differences between the two groups in terms of serum drug levels, half‐life, and clearance.…”

Preparation of Erythromycin Analogs Having Functional Groups at C-15

“…Flurithromycin, (8S)-8-fluoroerythromycin A, had higher serum and tissue levels than erythromycin at similar doses, demonstrative of the beneficial pharmacological effect of fluorination on the macrolide molecule [14]. Measurement of partitioning between 1-octanol and water at pH 7.4 indicates that 2 (log DХ0.3) is significantly less lipophilic than 1 (log DХ0.9).…”