This document discusses benzimidazole (BZDs), a class of broad-spectrum anthelminthic drugs used to control gastrointestinal nematodes in livestock and as an antiparasitic in agriculture. BZDs work by inhibiting microtubule synthesis in nematode cells, disrupting cell division and function. They are relatively safe for use in animals due to differences in tubulin binding sites between nematodes and vertebrates. Common BZDs include albendazole, fenbendazole, and oxfendazole, which are administered orally and have limited water solubility requiring special formulations. They are metabolized and excreted slowly, persisting in the body for weeks. Resistance can develop through mutations

1. Benzimedazole
(BZDS)
Benzimidazole
(BZDS)
Presented by : Dr. Azhar Memon
M.Phil Scholar
Dept of Vet: Parasitology

2. Benzimidazole- Introduction-1912
 Pharmacological Agent.
 Bicyclic consists of the fusion of benzene and imidazole
 Most prominent benzimidazole compound in nature is N-ribosyl-
dimethylbenzimidazole.
 Presence of benzimidazole nucleus in numerous categories of
therapeutic agents for development of new therapeutic agents
 Antimicrobials
 Antivirals,
 Antiparasitic,
 Anticancer,
 Anti-inflammatory,
 Antioxidants,
 Proton pump inhibitors,
 Antihypertensives,
 Anticoagulants,
 Immunomodulators,
 Hormone modulators,
 CNS stimulants
 CNS depressants,
 Lipid level modulators,
 Antidiabetics, etc

3. Benzimidazole- Antiparasitic
 Group of Broad-Spectrum anthelminthic drugs
 Nematocidal drug
 Primarily used for the control of GI nematodes not
only for livestock's (Cattle, Sheep, Goat, Swine and
Poultry) but also Horse, dog, cat and human as
well.
 Also used in agriculture to control the helminth
parasite in plants.
 Before 1960s Benzimidazoles are used as fungicide
in plants.
 Worldwide use over a four decades due to its
safety and spectrum.

4. Include
 Benzimidazole Thiazolyls
 Thiabendazole (TBZ) - Prototype
 Cambendazole
 Probenzimidazole- Prodrug :-
 Netobimin (NTB)
 Febantel (FBT) – Dogs and cats
 Halogenated benzimidazole:
 Triclabendazole (Flukicidal)
 Benzimidazole methyl carbamate:
 Albendazole (ABZ)-Cattle
 Fenbendazole (FBZ)-Cattle, Horse,
dogs and cats
 Oxfendazole (OFZ) –Cattle and
Horse
 Flubendazole (FLBZ) – Poultry and
Pigs
 Mebendazole (MBZ)- Dogs and Cats
 Parbendazole
 oxibendazole

5. Chemistry
 All of BZDs,, have a side chain at
position 2 and 5, which prevents
hydroxylation of position 5 of the BZD.
Therefore, these compounds are more
potent than thiabendazole as
nematicides
 except thiabendazole
 It has been postulated that the
presence of a carbamate group in the
2- position is essential for potent
microtubule inhibitory activity.

6. MOA
 BZDs inhibit microtubule
synthesis in nematode cells by
interfering with
polymerization of β-tubulins
 Microtubule are hollow
tubular organelle that is
composed of dimeric protein
comprised of α and β subunit.
used for
 Cell division,
 Maintenance of cell shape,
 Cell motility,
 Cell secretion,
 Nutrient absorption
 Intracellular transport.

7. MOA
The microtubule loss observed at
 tegumental
 intestinal level in cestodes and nematodes
followed by
 loss of transport of secretory vesicles
 decreased glucose uptake.
 Additionally,
 the inhibition of secretion of nematode acetylcholinesterase
 some enzymatic activities (such as fumarate reductase, malate dehydrogenase,
phosphoenol pyruvate reductase, and succinate dehydrogenase)
 BZDs do not affect microtubule synthesis in animal cells, therefore these drugs are
relatively safe in animals- Rate constant for dissociation.

8. BZ-susceptible nematodes have the amino acid
 Phenylalanine at positions 167 and 200,
 Glutamate at position 198 of the ß tubulin protein and this results in a
high affinity binding site for BZs.
In contrast, vertebrates
commonly have tyrosine at codon 200, and lack a high affinity BZ
binding site and are not susceptible to significant toxicity from BZ
drugs.
Why these drugs does not affects the Vertebrates……?

9. Administration
lack of water solubility is an important
limitation for the formulation of BZD
compounds, which mainly allows their
preparation as
 suspensions,
 pastes, or
 granules for
 orally or intraruminal administration
 One dose in Cattle and horses
 2-3 doses to the carnivores and
omnivores.

10. Pharmacokinetics
Absorption:-
 Absorption depend upon water solubility.
 Methylcarbamate's BZD have only limited water
solubility and small differences in drug solubility may
have a major influence on their absorption and
resultant pharmacokinetic behavior.
 Poor absorption.
 Albendazole and oxfendazole have better GI
absorption
 Animal should feed fiber before oral dose because
BZDs bind to fiber to preventing them from passing
through the GIT Tract and Facilitating absorption.

11. Metabolism and Excretion :-
All BZDs except thiabendazole are resistant to metabolism.
Parent Drug (TBZ) is short lived and metabolic products predominate in plasma and
all tissues and excreta of the host, as well as in parasites recovered from BZD-
treated animals.
Other Drugs: Pass first pass metabolism in Intestinal, liver, and lung metabolism in
most of animals.
Additionally GI metabolism is an important concern in ruminant species.
Phase I: Primary Metabolites:
Oxidative and hydrolytic processes and are all more polar and water soluble than
the parent drug.
Phase II: Primary metabolites are conjugated with glucuronide and/or sulfate to
increase their polarities, which facilitates urinary or biliary excretion.
Albendazole are converted to its sulfone, sulfoxide metabolites which are active.
Pharmacokinetics

12. Pharmacokinetics

13. Mechanisms of Drug Transfer into Target Parasite

14. After oral administration
BZDs
Tmax - 10-20hrs
Elimination
 Albendazole : 9-14 hrs.
 Febendazole: 27-36 hrs.
 Oxfendazole : 18 hrs.
Drug Residue: Persist 1-3 weeks.
With drawl period :
 Albendazole : 27 days
 Oxfendazole : 7 days
 Febendazole : 8 Days
Donot use in dairy lactating cattle except
Fenbendazole

15. Therapeutic Uses

16. Resistance
 Cross Resistance
 loss of high affinity BZ-parasite tubulin
interactions.
 MOA:
 Mutation:-,
 At codon 167 and 200 (phenylalanine to
tyrosine),
 sometimes at codon 198 (glutamate to
alanine) result in BZ resistance

17. Adverse Effect
 Safe
 Except Albendazole have teratogenic and
embryotoxic effect.
 In High dose cause toxicity in liver and bone
marrow

18. `