Chemical Properties
White Solid
Usage
Roxithromycin was one of the new generation erythromycins introduced in the 1980s. Improved acid stability was achieved by converting the 9-keto group to the more stable oxime and alkylation of the oxime to provide the methoxyethoxymethyl ether oxime. In vivo, roxithromycin exhibits higher tissue levels and a longer half-life while being slightly less potent than erythromycin in vitro.
Usage
Semisynthetic erythromycin derivative. Antibacterial
Brand name
Rulide (Hoechst-Roussel).
Description
Roxithromycin, an oxime ether derivative of erythromycin, is a new macrolide antibiotic
of high potency and long duration. Its in v i m activity spectrum is similar to that of
erythromycin, but is superior to the latter against Legionella, Mycoplasma and Chlamydia.
Originator
Roussel (France)
Definition
ChEBI: Roxithromycin is semisynthetic derivative of erythromycin A. It has a role as an antibacterial drug. It is an erythromycin derivative, a macrolide and a semisynthetic derivative. It is functionally related to an erythromycin A.
Antimicrobial activity
Activity against common pathogens is comparable to that of erythromycin. It is active against L. monocytogenes, C. jejuni, H. ducreyi, G. vaginalis, Bord. pertussis, C. diphtheriae, B. burgdorferi, H. pylori, the M. avium complex, Chlamydia spp., and U. urealyticum.
Pharmaceutical Applications
A semisynthetic derivative of erythromycin A formulated for oral use.
Pharmacokinetics
Oral absorption：50–55%
Cmax 150 mg oral ： 7.9 mg/L after 1.9 h
300 mg oral ：10.8 mg/L after 1.5 h
Plasma half-life ：10.5–11.9 h
Plasma protein binding ：c. 90%
absorption and metabolism
Absorption is not affected by food. Oral administration with antacids or H2-receptor antagonists does not significantly affect bioavailability. In a direct comparison, the area under the time–concentration curve (AUC) produced by a 150 mg dose was 16 times greater than that produced by 250 mg erythromycin A. Behavior in children is broadly similar to that in adults, repeated doses of 2.5 mg/kg producing age-independent mean peak plasma concentrations around 10 mg/L at 1–2 h, but the apparent elimination half-life was longer (approximately 20 h).
It is saturably bound to α-acid glycoprotein in plasma. The plasma clearance appears to be dose dependent or plasma concentration dependent.
DistributionIt is widely distributed, but does not reach the CSF. Concentrations close to the simultaneous serum level have been found in tonsillar, lung, prostatic and other tissues. It achieves high levels in skin.
Distribution
It is widely distributed, but does not reach the CSF. Concentrations close to the simultaneous serum level have been found in tonsillar, lung, prostatic and other tissues. It achieves high levels in skin.
Metabolism and excretion
Less than 5% of the administered dose is eliminated as degradation products. Rather more than half the dose appears in the feces and only 7–10% (including metabolites) in the urine： up to 15% is eliminated via the lungs. Renal clearance increased in volunteers as the dose was raised from 150 to 450 mg,
and is decreased in elderly subjects. In patients in whom the creatinine clearance was <10 mL/min, the apparent elimination half-life rose to around 15.5 h and total body clearance was significantly reduced. The apparent elimination half-life was somewhat increased in patients with hepatic cirrhosis.
Side effects
It is generally well tolerated, adverse effects being described in 3–4% of patients, mostly gastrointestinal disturbance (abdominal pain, nausea and diarrhea). Headache, weakness, dizziness, rash and reversible changes in liver function tests and increased eosinophils and platelets have also been described.
