Drug absorption living tissues

Absorption is reduced by food and antacids and the drug should be taken on an empty stomach. Peak plasma concentrations are reached within 1-2 hours. It is widely distributed to all tissues and fluids, including the CNS. INH has a low protein binding of less than 10%. It is eliminated mainly by acetylation in the liver. In rapid acetylators half-lives of 0.5-1.6 hours are found while slow acetylators show half-lives of 2-5 hours. A minor metabolic pathway is via hydroxylation. 

Doxycycline and minocycline are more lipophilic tetracyclines. They are well absorbed after oral administration. Their half-lives are 16-18 hours. Their higher affinity for fatty tissues improves their effectiveness and changes their adverse effects profile. Local gastrointestinal irritation and disturbance of the intestinal bacterial flora occur less often than with the more hydrophilic drugs, which have to be given in higher oral doses for sufficient absorption. 

Contralateral tissue drug levels were <1% of those in the treated eye. Further, intravenous administration achieved <5% of the tissue levels attained after topical dosing. These results imply that systemic absorption and intraocular reentry are not significant routes of delivery. In animals where topical dosage was applied after sacrifice, there was no significant difference in intraocular drug levels compared to live animals. This implied that delivery by local vasculature was not a major component. 

B. Pharmacokinetics Oral absorption is variable, especially for the older drugs, and may be impaired by foods and multivalent cations (calcium, iron, aluminum). Tetracyclines have a wide tissue distribution and cross the placental barrier. All of the tetracyclines undergo entero-hepatic cycling. Doxycycline is excreted mainly in feces the other drugs are eliminated primarily in the urine. The half-lives of doxycycline and minocycline are longer than those of other tetracyclines. 

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