Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

ANTIPROTOZOAL DRUGS
Table 10.6 Clinical applications and dose rates of antiprotozoal drugs in dogs and cats
Class/Drug/Indications/Dose regimen/Comments
8-AMINOQUINOLINE
Act by generating reactive oxygen species or by interfering with electron transport.
Primaquine phosphate
Babesia felis 0.5 mg/kg PO on three occasions at intervals of 3 days
Identified during WWII in a systematic synthetic chemistry study to find safer 8-AQ antimalarial drugs. Low margin of safety in cats (has
caused death at 1 mg/kg). Clinical cure achieved but not sterilization of infection. Repeated or chronic therapy may be required. Little PK
information in dogs and cats, but in other species is well absorbed after oral administration with peak concentrations in 2–3 h, volume of
distribution greater than body water, extensive metabolism, elimination half-life of parent drug of 6 h and excretion of metabolites in urine.
Toxic effects include methemoglobinemia and hemolysis in face of G6PD deficiency.
AMINOACRIDINE
Aminoacridines intercalate readily with giardial DNA leading to inhibition of nucleic acid synthesis. However, differing relative drug uptake
rates between mammalian and giardial cells may account for selective toxicity.
Quinacrine (mepacrine) hydrochloride
Giardiosis 6.6 mg/kg PO q.12 h for 3–5 days
Bitter tasting. Absorbed rapidly from gastrointestinal tract, distributed widely, concentrates in liver, spleen, lungs and adrenal glands. Peak
concentrations within 8–12 h, elimination half-life up to 14 days with excretion principally in urine. Adverse effects include anemia, vomiting
and diarrhea. Nonclinically important yellow discoloration of skin and urine common. Lowest adverse intravenous dose in cat reported as
10 mg/kg.
AROMATIC DIAMIDINE
The specific mode of action of the aromatic diamidines is unclear. However, transmembrane transport proteins (especially the high affinity
purine 2 (P2) transporter) actively accumulate aromatic diamidines within susceptible protozoa. As di-cations (and therefore poorly
absorbed after oral administration), aromatic diamines also interact electrostatically with cellular polyanions, in particular with AT-rich
regions of RNA and DNA acid duplexes via intercalation and minor-groove binding, leading to structural disorganization (especially
unwinding) of kinetoplast supercoiled DNA and inhibition of replication, RNA polymerization and protein synthesis. Other potentially toxic
effects arise from action on multiple cellular targets including inhibition of synthesis of trypanothione, a vital cofactor in kinetoplast function,
reduction in mitochondrial membrane potential and selective inhibition of plasma membrane Ca 2+ -ATPase. Reducing inositol uptake by
host erythrocytes may lead to energy deprivation and death of parasitic Babesia.
Diminazene diaceturate
(preparations often contain 55% antipyrine to stabilize 45% diminazine in aqueous environment)
Babesia canis/gibsoni 3.5–4.2 mg/kg IM
Trypanosoma brucei/congolense 3.5–7 mg/kg IM q.14 days
Hepatozoon canis 3.5 mg/kg IM
Cytauxzoon felis 2 mg/kg IM twice at interval of 7 days
The pharmacokinetics of diminazene following IM injection in the dog show marked interanimal variability. Absorption is rapid with
T max at 20 min. There is rapid distribution and concentration in the liver from where slow redistribution to tissues takes place. After IV
administration, the elimination half-life was up to 60 h. Adverse effects in dogs include nervous signs, anaphylaxis and vomiting. Cats
appear to be more sensitive than dogs to diminazene.
Imidocarb dipropionate
Babesia canis/gibsoni 2–6.6 mg/kg SC or IM twice at interval of 14 days (may also protect from reinfection for 2–6 weeks)
Hepatozoon canis 5 mg/kg SC once; or imidocarb 5 mg/kg SC q.14 days + doxycycline 10 mg/kg PO q.24 h 14 days
The pharmacokinetics after IV administration were biphasic with a large volume of distribution. The mean terminal half-life was 207 min. The
margin of safety is low, with doses of 9.9 mg/kg. Pain on injection, local reactions, salivation, vomiting and anaphylaxis are most frequently
reported adverse signs. Atropine preadministration can limit cholinergic signs. At lower dose rates clinical cure is more likely than
parasitological cure and relapse is possible. In endemic areas, parasitological cure is not recommended. In the presence of endotoxininduced
fever in dogs, the volume of distribution and clearance are decreased with no change in elimination half-life. Imidocarb has been
shown to block LPS-induced TNF-α production and to increase serum IL-10 levels, novel anti-inflammatory actions that may contribute to
its antiprotozoal activity.
Pentamidine
Pneumocystis carinii (jiroveci) 4 mg/kg IM q.24 h 3 weeks
Babesia gibsoni/canis 16.5 mg/kg IM q.24 h 2 days
Leishmaniosis 4 mg/kg IM q.48 h 30–40 days
Pentamidine is well absorbed after IM administration concentrating in a variety of tissues, particularly the liver, kidney and spleen, from where
the drug dissipates slowly over a period of many weeks. Adverse effects associated with treatment include pain at the injection site,
hyoptension, vomiting, diarrhea, hypoglycemia, diabetes mellitus, hypocalcemia and renal failure.
Phenamidine isethionate
Alternative to pentamidine for treatment of Babesia gibsoni 7.5–15 mg/kg IM, SC q.24 h 1–2 days
Usually well tolerated but some dogs may have a temporary hypersensitivity reaction with salivation, vomiting and diarrhea, and facial
swelling. Concurrent use of cholinesterase inhibitors is contraindicated.
AZO DYE
Mode of action may involve DNA intercalation and inhibition of protein synthesis and cell replication.
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