Biomaterial Database

Predicting in vivo absorption of chloramphenicol in frogs using in vitro percutaneous absorption data. 2021

Victoria K Llewelyn, and Lee Berger, and Beverley D Glass

Pharmacy, College of Medicine and Dentistry, James Cook University, Townsville, Australia. victoria.llewelyn@my.jcu.edu.au.

BACKGROUND Infectious disease, particularly the fungal disease chytridiomycosis (caused by Batrachochytrium dendrobatidis), is a primary cause of amphibian declines and extinctions worldwide. The transdermal route, although offering a simple option for drug administration in frogs, is complicated by the lack of knowledge regarding percutaneous absorption kinetics. This study builds on our previous studies in frogs, to formulate and predict the percutaneous absorption of a drug for the treatment of infectious disease in frogs. Chloramphenicol, a drug with reported efficacy in the treatment of infectious disease including Batrachochytrium dendrobatidis, was formulated with 20% v/v propylene glycol and applied to the ventral pelvis of Rhinella marina for up to 6 h. Serum samples were taken during and up to 18 h following exposure, quantified for chloramphenicol content, and pharmacokinetic parameters were estimated using non-compartmental analysis. RESULTS Serum levels of chloramphenicol reached the minimum inhibitory concentration (MIC; 12.5 μg.mL- 1) for Batrachochytrium dendrobatidis within 90-120 min of exposure commencing, and remained above the MIC for the remaining exposure time. Cmax (17.09 ± 2.81 μg.mL- 1) was reached at 2 h, while elimination was long (t1/2 = 18.68 h). CONCLUSIONS The model, based on in vitro data and adjusted for formulation components and in vivo data, was effective in predicting chloramphenicol flux to ensure the MIC for Batrachochytrium dendrobatidis was reached, with serum levels being well above the MICs for other common bacterial pathogens in frogs. Chloramphenicol's extended elimination means that a 6-h bath may be adequate to maintain serum levels for up to 24 h. We suggest trialling a reduction of the currently-recommended continuous (23 h/day for 21-35 days) chloramphenicol bathing for chytrid infection with this formulation.

UI	MeSH Term	Description	Entries
D008826	Microbial Sensitivity Tests	Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).	Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D002024	Bufo marinus	A species of the true toads, Bufonidae, becoming fairly common in the southern United States and almost pantropical. The secretions from the skin glands of this species are very toxic to animals.	Rhinella marina,Toad, Giant,Toad, Marine,Giant Toad,Giant Toads,Marine Toad,Marine Toads,Toads, Giant,Toads, Marine
D002701	Chloramphenicol	An antibiotic first isolated from cultures of Streptomyces venequelae in 1947 but now produced synthetically. It has a relatively simple structure and was the first broad-spectrum antibiotic to be discovered. It acts by interfering with bacterial protein synthesis and is mainly bacteriostatic. (From Martindale, The Extra Pharmacopoeia, 29th ed, p106)	Cloranfenicol,Kloramfenikol,Levomycetin,Amphenicol,Amphenicols,Chlornitromycin,Chlorocid,Chloromycetin,Detreomycin,Ophthochlor,Syntomycin
D000084662	Batrachochytrium	A genus of fungi in the order Rhizophydiales, class Chytridiomycetes and phylum CHYTRIDIOMYCOTA. Batrachochytrium fungi are chytrid fungi found in aquatic habitats. Many are parasitic including Batrachochytrium dendrobatidis which is causative agent for chytrid disease in aquatic invertebrates.	Batrachochytrium dendrobatidis
D000279	Administration, Cutaneous	The application of suitable drug dosage forms to the skin for either local or systemic effects.	Cutaneous Drug Administration,Dermal Drug Administration,Drug Administration, Dermal,Percutaneous Administration,Skin Drug Administration,Transcutaneous Administration,Transdermal Administration,Administration, Dermal,Administration, Transcutaneous,Administration, Transdermal,Cutaneous Administration,Cutaneous Administration, Drug,Dermal Administration,Drug Administration, Cutaneous,Skin Administration, Drug,Administration, Cutaneous Drug,Administration, Dermal Drug,Administration, Percutaneous,Administrations, Cutaneous,Administrations, Cutaneous Drug,Administrations, Dermal,Administrations, Dermal Drug,Administrations, Percutaneous,Administrations, Transcutaneous,Administrations, Transdermal,Cutaneous Administrations,Cutaneous Administrations, Drug,Cutaneous Drug Administrations,Dermal Administrations,Dermal Drug Administrations,Drug Administrations, Cutaneous,Drug Administrations, Dermal,Drug Skin Administrations,Percutaneous Administrations,Skin Administrations, Drug,Skin Drug Administrations,Transcutaneous Administrations,Transdermal Administrations
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000900	Anti-Bacterial Agents	Substances that inhibit the growth or reproduction of BACTERIA.	Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D012869	Skin Absorption	Uptake of substances through the SKIN.	Absorption, Skin,Intracutaneous Absorption,Intradermal Absorption,Percutaneous Absorption,Transcutaneous Absorption,Transdermal Absorption,Absorption, Intracutaneous,Absorption, Intradermal,Absorption, Percutaneous,Absorption, Transcutaneous,Absorption, Transdermal,Absorptions, Intracutaneous,Absorptions, Intradermal,Absorptions, Percutaneous,Absorptions, Skin,Absorptions, Transcutaneous,Absorptions, Transdermal,Intracutaneous Absorptions,Intradermal Absorptions,Percutaneous Absorptions,Skin Absorptions,Transcutaneous Absorptions,Transdermal Absorptions