Pharmacological Effects Of Roxithromycinde
Pharmacological Action
Roxithromycin is a new generation of macrolide antibiotics, a semi synthetic 14 membered macrolide drug. Its mechanism of action is the same as that of erythromycin. It mainly binds to bacterial 50S ribosome subunit, and inhibits bacterial protein synthesis by blocking peptide transfer and mRNA translocation, thus playing an antibacterial role. Its characteristic is that it can quickly enter macrophages, lung cells, alveoli, and polymorphonuclear white blood cells. The antibacterial spectrum of roxithromycin is similar to that of erythromycin, and its in vitro antibacterial effect is similar to that of erythromycin. The in vivo antibacterial effect is 1-4 times stronger than that of erythromycin. Roxithromycin has a slightly weaker effect on Gram positive bacteria than erythromycin, and a stronger effect on Legionella pneumophila than erythromycin. The antimicrobial activity against Chlamydia pneumoniae, Mycoplasma pneumoniae, and Ureaplasma urealyticum is similar to or slightly stronger than that of erythromycin. Roxithromycin has strong antibacterial activity against Staphylococcus aureus (except MRSA), streptococci (including Type A, B, C streptococci and Streptococcus pneumoniae, but excluding Type G and Enterococcus), Corynebacterium, Listeria, Catamora (Catarrhococcus), Legionella, etc; It also has certain effect on oral Bacteroides, Bacteroides niger, digestive coccus, Peptostreptococcus, Propionibacterium acnes and other anaerobic bacteria, as well as toxoplasma encephalitis, chlamydia, mycoplasma, ureaplasma urealyticum, treponema pallidum, etc; It has weak effect on helicobacter, gonococcus, meningococcus, Bordetella pertussis, etc. Roxithromycin can inhibit most Gram positive bacteria, and its antibacterial activity against common pathogenic bacteria such as Staphylococcus aureus, Staphylococcus epidermidis, Pneumococcus, Streptococcus pyogenes, Influenza bacteria, Mycoplasma pneumoniae, and Legionella in respiratory and skin infections is similar to that of erythromycin. It is effective against urinary and reproductive system infections caused by Chlamydia trachomatis and Ureaplasma urealyticum, and against Treponema pallidum.
Pharmacokinetics
Roxithromycin is acid resistant and not damaged by gastric acid. It is well absorbed from the gastrointestinal tract and has a high blood concentration (the peak blood concentration of Roxithromycin is the highest among all macrolide drugs). After a single oral dose of 150mg, the blood drug concentration reached its peak after 2 hours, with an average of 6.6-7.9 μ g/mL。 After absorption, its distribution in tissues and body fluids is higher than that of erythromycin. The drug concentration in the tonsils, sinuses, middle ear, lungs, sputum, prostate, and other urogenital tissues can all reach effective therapeutic levels. But the content is very low in breast milk. The area under the drug concentration time curve (AUC) and peak blood drug concentration are directly proportional to the dose. The protein binding rate of roxithromycin is 96% at a blood concentration of 2.5mg/L, and the clearance half-life is 8.4-15.5h, which is much longer than erythromycin. The drugs are mainly excreted in their original form with feces, and some are also excreted as hypoglycemic metabolites. Another approximately 7.4% is excreted through urine. In patients with renal insufficiency, the half-life is prolonged and the area under the drug concentration time curve (AUC) increases. In patients with severe liver cirrhosis, the half-life can be extended by two times. The absorption rate of roxithromycin is not affected by age, and generally has few adverse reactions and low toxicity.
Drug interactions
1. The combination of roxithromycin and sulfamethoxazole (1:19) can increase the inhibitory effect on Haemophilus influenzae by 2-4 times, and the incidence of drug resistance can decrease from 47.2% to 10.0%.
2. When combined with proton pump inhibitors (such as lansoprazole and omeprazole), the systemic bioavailability of roxithromycin does not change, but it can increase the local concentration of roxithromycin in the stomach. This effect may help the combination of roxithromycin and proton pump inhibitors to eradicate Helicobacter pylori.
3. When used together with warfarin, roxithromycin may inhibit the metabolism of warfarin, increase the blood concentration of warfarin, and increase the risk of bleeding.
4. When combined with benzodiazepine drugs such as prazoram, diazepam, midazolam, and triazolam, roxithromycin can inhibit liver enzymes responsible for benzodiazepine metabolism, leading to an increase in blood concentration of benzodiazepine drugs by reducing clearance rate, prolonging half-life, and increasing distribution volume.
5. The combination of roxithromycin and pimozide may inhibit the metabolism of pimozide, leading to an increase in the blood concentration of the latter and causing certain cardiovascular adverse reactions, such as prolonged Q-T interval, arrhythmia, and sudden death.
6. When used together with digoxin, roxithromycin can clear the gut microbiota that can inactivate digoxin, leading to a decrease in digoxin degradation in the body and an increase in digoxin blood concentration, leading to toxic reactions.
7. The use of roxithromycin in combination with clopidogrel may lead to an increase in the blood concentration of clopidogrel.
8. The combination of roxithromycin and astemizole may lead to an increase in the blood concentration of astemizole.
9. Roxithromycin is used together with cyclosporine, and it may promote the absorption of cyclosporine and interfere with its metabolism, leading to an increase in the blood concentration of cyclosporine.
10. The combination of roxithromycin and ergotamine derivatives can cause acute ergot poisoning (such as peripheral vasospasm).
11. Taking roxithromycin together with birth control pills has no effect on the effectiveness of oral contraceptives.
12. Roxithromycin has little effect on carbamazepine and ranitidine.
13. The pharmacokinetic effect of roxithromycin on theophylline is similar to that of erythromycin, but it is relatively mild. It can prolong the half-life of theophylline by 8% and eliminate it by 16%. When used in combination with theophylline, the dosage of theophylline does not need to be reduced, but its drug concentration should be monitored.
14. Unlike erythromycin, roxithromycin has no effect on the pharmacokinetic parameters of carbamazepine and can be used simultaneously.
