MACROLIDE

1. AZITHROMYCIN
Pharmacokinetics :
A 500-mg dose of azithromycin produces relatively low serum concentrations of
approximately 0.4 mcg/mL. However, azithromycin penetrates into most tissues (except
cerebrospinal fluid) and phagocytic cells extremely well, with tissue concentrations
exceeding serum concentrations by 10- to 100-fold. The drug is slowly released from tissues
(tissue half-life of 2–4 days) to produce an elimination half-life approaching 3 days. These
unique properties permit once-daily dosing and shortening of the duration of treatment in
many cases. For example, a single 1-g dose of azithromycin is as effective as a 7-day course
of doxycycline for chlamydial cervicitis and urethritis.
Azithromycin is rapidly absorbed and well tolerated orally. It should be administered
1 hour before or 2 hours after meals. Aluminum and magnesium antacids do not alter
bioavailability but delay absorption and reduce peak serum concentrations. Because it has a
15-member (not 14-member) lactone ring, azithromycin does not inactivate cytochrome P450
enzymes and, therefore, is free of the drug interactions that occur with erythromycin and
clarithromycin.
Pharmacodinamics :
The antibacterial action of Azithromycin and other macrolides may be inhibitory or
bactericidal, particularly at higher concentrations, for susceptible organisms. Activity is
enhanced at alkaline pH. Inhibition of protein synthesis occurs via binding to the 50S
ribosomal RNA. The binding site is near the peptidyltransferase center, and peptide chain
elongation (ie, transpeptidation) is prevented by blocking of the polypeptide exit tunnel. As a
result, peptidyl-tRNA is dissociated from the ribosome.
Azithromycin 2.0 g and ceftriaxone 250 mg are equally effective in the treatment of
uncomplicated gonorrhea. Azithromycin was associated with a relatively high frequency of
gastrointestinal side effects and is expensive, but it has the advantages of oral administration
and efficacy against concomitant chlamydial infection.
Available on : Tablets, capsules, powder suspensions, eye drops
Dosage in Gonorrhea : 2 grams single-dose
Safety :
Azithromycin does not inactivate cytochrome P450 enzymes and, therefore, is free of
the drug interactions that occur with erythromycin and clarithromycin. In addition,
Azithromycin can cause interaction between several other drugs, including: Increased risk of
damage to heart muscle if used with pimozide; Increased serum concentration when used
with digoxin, ciclosporin, terfenadine, hexobarbital, and phenytoin; Decreased drug
absorption rate when used with antacids containing aluminum and magnesium.
Cost : Rp.15.221,00 / tablet.
2. SOLITHROMYCIN
Pharmacokinetics :
(i) Single-dose pharmacokinetics.
Across the dose range studied, mean Cmaxs ranged from 0.0223 /ml to 1.964
g/ml and increased in a greater than dose-proportional manner to 1,200 mg. The meant
1/2 increased from 3.16 to 7.42h over the 50 to 1,600-mg dose range. The median
Tmax occurred 1.5 to 6.0 h following drug administration, and there was a trend for
Tmax values to increase as the dose of solithromycin increased.
(ii) Food effect on bioavailability and pharmacokinetics.
Pharmacokinetics of solithromycinin the fed state were bioequivalent to those in
the fasted state and that food had no effect on the bioavailability of solithromycin
following a single oral dose of 400 mg (two 200-mg capsules).
(iii) Multiple-dose pharmacokinetics.
Following repeated once-daily oral administration for 7 days, plasma
solithromycin exposure again increased in a greater than dose-proportional manner
across the 200- to 600-mg dose range, with mean Cmax, ss and AUC values increasing
from 0.25 to 1.50 g/ml and 2.3 to 18.4 g h/ml, respectively. Solithromycin median
Tmax values were 3.5 to 4.0 h, and the harmonic mean t1/2 increased (from 5.8 to 8.7
h) for the 200-, 400-, and
600-mg doses.
With repeated once-
daily oral solithromycin
administration, the median
Tmax values remained
constant between day 1 and
day 7 over the dose range
studied (median ranges, 3 to
3.75 h and 3.50 to 4 h,
respectively).
At all doses,
solithromycin exposures
were higher on day 7 than on
day 1, indicating
accumulation over this
dosing period. AUC and
Cmaxs were 1.7 to 2.2 times
greater on day 7 than on day
1. The median AIs were
approximately 3, 2, and 2 for
the 200-, 400-, and 600-mg
doses, respectively.
Pharmacodinamics :
Solithromycin had superior
activity against gonococcal isolates
compared to activities of
azithromycin, other macrolides, and
many other classes of
antimicrobials. Solithromycin might
be an effective option for gonorrhea
treatment, as single-antimicrobial
treatment especially for ESC
(Extended-Spectrum
Cephalosporin) resistant cases and
in antimicrobial combination
therapy.
Available on : Capsule
Dosage : 50-400 mg in once a day (400mg = two-200 mg capsules)
Safety
Single oral doses of solithromycin were well tolerated at all dose levels. Single oral
doses of 400 mg (two 200-mg capsules) of solithromycin administered in the fasting and fed
states were generally well tolerated in the healthy adult subjects in the food effects-
bioavailability. Multiple-oral-dose regimens of solithromycin administered to healthy adult
subjects for 7 days were well tolerated at all dose levels. Clinical laboratory studies showed
normal pre-dosing and postdosing values in subjects at the 200- and 400-mg dose levels. Four
of 10 subjects administered 600 mg of solithromycin had low-level hepatic transaminase
increases (for ALT, 3 determinations at less than or equal 2 times the ULN and 1
determination at less than 3 times the ULN; for AST, 2 determinations at less than 2 times
theULN) during dosing that rapidly returned to normal values within 5 to 8 days after dosing
was completed. All other laboratory studies showed normal values, including serum bilirubin
determinations no associated clinical symptoms
Cost : $120.00 (Rp. 1.820.586,00) / 100 gram
 DAFTAR PUSTAKA

Bignell C., Unemo M.. 2013. 2012 European guideline on the diagnosis and treatment of
gonorrhoea in adults. Int. J. STD AIDS. Vol 24, pp 85–92.
Golparian D., Fernandes P., Ohnishi M., Jensen S. J., Unemo M.. 2012. In Vitro Activity of
the New Fluoroketolide Solithromycin (CEM-101) against a Large Collection of Clinical
Neisseria gonorrhoeae Isolates and International Reference Strains, Including Those with
High-Level Antimicrobial Resistance: Potential Treatment Option for Gonorrhea?. NCBI
PubMed. pp 2739–2742.
Handsfield H. H., Dalu Z. A., Martin D. H., Douglas J. M. Jr., McCarty J. M., Schlossberg
D.. 1994. Multicenter trial of single-dose azithromycin vs. ceftriaxone in the treatment of
uncomplicated gonorrhea. Azithromycin Gonorrhea Study Group. NCBI PubMed. Vol. 21,
no. 2, pp 107-111.
Katzung B. G.. 2014. Farmakologi Dasar dan Klinik, XII edition. Salemba Medika: Jakarta.
pp 813-814.
Still G. J., Scrahnz J., Scott D., et al. 2011. Pharmacokinetics of Solithromycin (CEM-101)
after Single or Multiple Oral Doses and Effects of Food on Single-Dose Bioavailability in
Healthy Adult Subjects. NCBI PubMed. Vol. 55, no. 5, pp 1997-2003.
[Online] at https://indonesian.alibaba.com/product-detail/solithromycin-760981-83-7-
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[Online] at http://www.alodokter.com/azithromycin
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