Clarithromycin
is acid stable rapidly and completely
absorbed per orally to the extent of
100% and absolute bioavailability is
55% and is unaffected by food.
Binding-
80% to Plasma alpha 1 acidic
glycoprotein
Vd
- 191 306 L
Plasma
t ½
-
3-4 hrs (Max 9 hrs)
Salivary
concentration =
Plasma concentration
Prolonged
high concentrations in -
Lungs, Tonsils, nasal tissue,
middle ear and
WBC (twice that of plasma).
Hepatic
metabolism & its 14 OH metabolite
is pharmacologically active
(synergistic activity renders it
bactericidal).
Clarithromycin
inhibits the isoenzyme of Cyt P 450
viz., CYP3A family and thereby
increase the concentrations of several
drugs administered concurrently
resulting in serious clinically
significant drug interactions. The
hepatic metabolism of clarithromycin
is reduced in older patients with
hepatic impairment and necessary dose
adjustments have to be made., however,
in mild
hepatic dysfunction no dose
adjustments need be necessary. Hepatic
elimination constitutes about 60% and
renal elimination about 37%. No dose
adjustments is necessary unless
creatinine clearance is < 30 ml/Mt.
i.e., 1.8L/hr. Clarithromycin
concentrations achieved in tissue
exceed the plasma by;
3.1
: 1 Bronchial secretion
8.82
: 1
Middle year fluid
5.17
: 1
Epithelial lining fluid
94.1
: 1
Alveolar macrophages
28.7
: 1
Lung tissue
331
:
1
Tonsillar tissue
27.5
: 1
Nasal mucosa.
Of
particular note is the high
concentration in the alveolar
macrophages, Lung tissue and tonsillar
tissue show high penetration of the
drug into the respiratory tract cells,
a feature that should enhance efficacy
against typical and atypical pathogens
which usually cause community acquired
pneumonia ( CAP). Concentrations of
both clarithromycin and its 14 OH
metabolite (active) exceed MICs for
most respiratory pathogens maintained
longer in tissue than fluid and longer
in fluid secretions than in plasma.
Significant
quantities of clarithromycin and its
metabolites are excreted in breast
milk of nursing mothers.
A
Modified Release (MR) formulation of
clarithromycin has been developed to
increase the patient compliance and
the elimination t ½ of clarithromycin
and its metabolite is not
altered although the peak
concentrations may be delayed.
