<unk>  is extremely lipid-soluble; it remains relatively unbound to protein and is a small molecule. It has a large apparent volume of distribution and penetrates effectively into all tissues of the body, including the brain. Distribution is not uniform, with highest concentrations found in the liver and kidney, with lowest in the brain and cerebrospinal fluid. The concentration achieved in brain and cerebrospinal fluid is around 30 to 50% of the overall average body concentration, even when the meninges are not inflamed; this increases to as high as 89% when the meninges are inflamed.<unk>  increases the absorption of iron. Use in special populations<unk>  is metabolized by the liver to<unk>  glucuronate (which is inactive). In liver impairment, the dose of<unk>  must therefore be reduced. No standard dose reduction exists for<unk>  in liver impairment, and the dose should be adjusted according to measured plasma concentrations. The majority of the<unk>  dose is excreted by the kidneys as the inactive metabolite,<unk>  glucuronate. Only a tiny fraction of the<unk>  is excreted by the kidneys unchanged. Plasma levels should be monitored in patients with renal impairment, but this is not mandatory.<unk>  succinate ester (an intravenous prodrug form) is readily excreted unchanged by the kidneys, more so than<unk>  base, and this is the major reason why levels of<unk>  in the blood are much lower when given intravenously than orally.<unk>  passes into breast milk, so should therefore be avoided during breast feeding, if possible. Dose monitoring Plasma levels of<unk>  must be monitored in neonates and patients with abnormal liver function. Plasma levels should be monitored in all children under the age of four, the elderly, and patients with kidney failure. Because efficacy and toxicity of<unk>  are associated with a maximum serum concentration, peak levels (one hour after the intravenous dose is given) should be 10–20 µg/ml with toxicity ; trough levels (taken immediately before a dose) should be 5–10 µg/ml. Drug interactions Administration of<unk>  concomitantly with bone marrow depressant drugs is contraindicated, although concerns over aplastic anaemia associated with ocular<unk>  have largely been discounted.<unk>  is a potent inhibitor of the cytochrome P450 isoforms CYP2C19 and CYP3A4 in the liver. Inhibition of CYP2C19 causes decreased metabolism and therefore increased levels of, for example, antidepressants, antiepileptics, proton-pump inhibitors, and anticoagulants if they are given concomitantly. Inhibition of CYP3A4 causes increased levels of, for example, calcium channel blockers, immunosuppressants, chemotherapeutic drugs, benzodiazepines, azole antifungals, tricyclic antidepressants, macrolide antibiotics, SSRIs, statins, cardiac antiarrhythmics, antivirals, anticoagulants, and PDE5 inhibitors. Drug antagonistic<unk>  is antagonistic with most cephalosporins and using both together should be avoided in the treatment of infections.
Chloramphenicol
Tetracycline
Thiamphenicol
Minocycline
Natamycin
Meropenem
Methicillin
Amikacin