Klacid/Klacid MR

Klacid/Klacid MR Mechanism of Action





Zuellig Pharma
Full Prescribing Info
Clarithromycin is an antibiotic of the macrolide family.
Pharmacokinetics: Initial pharmacokinetic data were obtained with clarithromycin tablet formulations. These data indicated the drug is rapidly absorbed from the gastrointestinal tract and the absolute bioavailability of a clarithromycin 250-mg tab was approximately 50%. Both the onset of absorption and the formation of the antimicrobially active metabolite, 14-OH-clarithromycin, were slightly delayed by food, but the extent of bioavailability was not affected by administration of drug in the non-fasting state. In fasting healthy human subjects, peak serum concentrations were attained within 2 hrs after oral dosing. With twice-daily dosing using a 250-mg tab every 12 hrs, steady-state peak serum concentrations of clarithromycin were attained in 2-3 days and were approximately 1 mcg/mL. Corresponding peak serum concentrations were 2-3 mcg/mL with a 500-mg dose administered every 12 hrs. The elimination half-life of clarithromycin was about 3-4 hrs with a 250-mg tab administered every 12 hrs but increased to 5-7 hrs with 500 mg administered every 12 hrs. The principal metabolite, 14-OH-clarithromycin, attains a peak steady-state concentration of about 0.6 mcg/mL and has an elimination half-life of 5-6 hrs after a dose of 250 mg every 12 hrs. With a dose of 500 mg every 12 hrs, the peak steady-state concentrations of 14-OH-clarithromycin are slightly higher (up to 1 mcg/mL), and its elimination half-life is about 7 hrs. With either dose, the steady-state concentration of this metabolite is generally attained within 2-3 days. The steady-state concentrations of clarithromycin in subjects with impaired hepatic function did not differ from those of normal subjects; however, the 14-OH-clarithromycin concentrations were lower in the hepatically impaired subjects. The decreased formation of 14-OH-clarithromycin was at least partially offset by an increase in renal clearance of clarithromycin in the subjects with impaired hepatic function when compared to healthy subjects. The pharmacokinetics of clarithromycin were also altered in subjects with impaired renal function who received multiple 500-mg oral doses. The plasma levels, half-life, Cmax and Cmin for both clarithromycin and its 14-OH metabolite were higher and the AUC was larger in subjects with renal impairment than in normal subjects. The extent to which these parameters differed was correlated with the degree of renal impairment; the more severe the renal impairment, the more significant the difference. (See Dosage & Administration.) Clarithromycin and its 14-OH metabolite distribute readily into body tissues and fluids. Concentrations in tissues are usually several folds higher than serum concentrations. The bioavailability and pharmacokinetics of clarithromycin paediatric suspensions were investigated in adult subjects and in paediatric patients. A single-dose study in adult subjects found the overall bioavailability of the paediatric formulation to be equivalent to or slightly greater than that of the tablet (dosage with each was 250 mg). As with the tablet, administration of the paediatric formulation with food leads to a slight delay in the onset of absorption, but does not affect the overall bioavailability of clarithromycin. The comparative clarithromycin Cmax, AUC and T½ for the paediatric formulation (nonfasted state) were 0.95 mcg/mL, 6.5 mcg hr/mL and 3.7 hrs, respectively, and for the 250-mg tab (fasted state) were 1.1 mcg/mL, 6.3 mcg hr/mL and 3.3 hrs, respectively. In a multiple dose study in which adult subjects were administered 250 mg of the clarithromycin paediatric suspension every 12 hrs, steady state blood levels were nearly reached by time of the 5th dose. Pharmacokinetic parameters after the 5th dose for clarithromycin paediatric suspension were: Cmax 1.98 mcg/mL, AUC 11.5 mcg hr/mL, Tmax 2.8 hrs and T½ 3.2 hrs for clarithromycin, and 0.67, 5.33, 2.9 and 4.9, respectively, for 14-OH-clarithromycin. In paediatric patients requiring oral antibiotic treatment, clarithromycin demonstrated good bioavailability with pharmacokinetic profile, consistent with previous results from adult subjects using the same suspension formulation. The results indicated rapid and extensive drug absorption in children and, except for a slight delay in onset of absorption, food seemed to have no significant effect on drug bioavailability or pharmacokinetic profiles. Steady-state pharmacokinetic parameters obtained after the 9th dose on treatment day 5 were as follows for the parent drug: Cmax 4.6 mcg/mL, AUC 15.7 mcg hr/mL and Tmax 2.8 hrs; the corresponding values for the 14-OH metabolite were: 1.64 mcg/mL, 6.69 mcg hr/mL and 2.7 hrs, respectively. Elimination half-life was estimated to be approximately 2.2 and 4.3 hrs for the parent compound and metabolite, respectively. In another study, information was obtained regarding the penetration of clarithromycin in middle ear fluid in patients with otitis media. Approximately 2.5 hrs after receiving the 5th dose (dosage was 7.5 mg/kg twice daily), the mean concentration of clarithromycin was 2.53 mcg/g fluid in the middle ear and for the 14-OH metabolite was 1.27 mcg/g. The concentrations of parent drug and 14-OH metabolite were generally twice as high as the corresponding concentrations in serum.
Microbiology: Clarithromycin exerts its antibacterial activity by inhibiting the synthesis of proteins, by means of a link with the 50S sub-unit of the cellular ribosome. Clarithromycin has demonstrated excellent in vitro activity against both standard strains of bacteria and clinical isolates. It is highly potent against a wide variety of aerobic and anaerobic gram-positive and gram-negative organisms. The in vitro antibacterial spectrum of clarithromycin is as follows: Usually Sensitive Bacteria: Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus viridans, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Neisseria gonorrheae, Listeria monocytogenes, Legionella pneumophila, Pasteurella multocida, Mycoplasma pneumoniae, Helicobacter (Campylobacter) pylori, Campylobacter jejuni, Chlamydia trachomatis, Chlamydia pneumoniae (TWAR), Moraxella (Branhaemella) catarrhalis, Bordetella pertussis, Borrelia burgdorferi, Staphylococcus aureus, Clostridium perfringens, Peptococcus niger, Propionibacterium acnes, Bacteroides melaninogenicus, Mycobacterium avium, Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium intracellulare.
Nonsensitive Bacteria: Enterobacteriaceae, Pseudomonas sp.
The principal metabolite of clarithromycin in man and other primates is a microbiologically active metabolite, 14-OH-clarithromycin. This metabolite is as active or 1- to 2-fold less active than the parent compound for most organisms, except for H. influenzae against which it is twice as active. The parent compound and the 14-OH-metabolite exert either an additive or synergistic effect on H. influenzae in vitro and in vivo, depending on bacterial strains.
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