Page 109 - 80 guidelines for the treatment of malaria_opt

N
N
CI
2
CH 3
NH
CH 3
2
F HN H 3 C N CH 3 CI HN OH N CH 3 CH 3 H N O S O N H N O N O CH 3 H N N N 2 CH 3 CI
H 3 C H 3 C H 3 C
F F
F
F ANNEX 3. Pharmacology of antimalarial medicines
N O O O
O C O C O C
F O O O
ÿ O CH 3 O CH 3 Formulations O O CH 3
H H H H 3 C H H HO H H
O
HO O O • Capsules and tablets containing 100 mg of doxycycline salt as hydrochloride.
H H H
HN CH 3 CH 3 Pharmacokinetics CH 3
O
Doxycycline is readily and almost completely absorbed from the gastrointestinal tract
and absorption is not affected significantly by the presence of food. Peak plasma
H 3 C H 3 C CI concentrations occur 2 h after administration. Some 80–95% is protein-bound and half-
life is 10–24 h (78). It is widely distributed in body tissues and fluids. In patients with
CH 3
O O normal renal function, 40% of doxycycline is excreted in the urine, although more if the
O C O C HN NH 2 A3
O O urine is alkalinized. It may accumulate in renal failure. However, the majority of the dose
CH 3 CH 3 CI CI N
O O is excreted in the faeces.
H H H H
H 3 C H 3 C
HO H 3 C O Toxicity O
H H
CH 3 CH 3 H 3 C N As for tetracycline. Gastrointestinal effects are fewer than with tetracycline, although
OH
oesophageal ulceration can still be a problem if insufficient water is taken with tablets
or capsules. There is less accumulation in patients with renal impairment. Doxycycline
should not be given to pregnant or lactating women, or children aged up to 8 years.
CI CI Drug interactions
H H H
N N N CH 3 CI O
H NH NH CH 3 Doxycycline has a lower affinity for binding with calcium than other tetracyclines, so
H N S NH 2
2
NH NH CH 3 may be taken with food or milk. However, antacids and iron may still affect absorption.
O
CI H H H Metabolism may be accelerated by drugs that induce hepatic enzymes, such as
O N N N CH 3
carbamazepine, phenytoin, phenobarbital and rifampicin, and by chronic alcohol use.
H
OH
O
a3.14 clindamycin
Molecular weight: 425.0
Clindamycin is a lincosamide
H 2 C H H 3 C CH 3 OH CI
HO CH 3 H N OH O O O CH 3 O CH 3 antibiotic, i.e. a chlorinated
OH OH N derivative of lincomycin. It is very
NH N soluble in water. It inhibits the
N 2 H H
H 3 C O
HO H NH 2 CH 3 early stages of protein synthesis by
OH H HO S a mechanism similar to that of the
OH H H
O OH O OH O O macrolides. It may be administered
H 3 C H 3 C OH N HO OH by mouth as capsules containing
H 3 C CH 3 the hydrochloride or as oral liquid
N
preparations containing the palmitate
hydrochloride.

95