Fusidic acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

Clinical overview

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Objective of study:

other: Pharmacokinetics

Principles of method if other than guideline:

Clinical studies on orally administrated fusidic acid in humans.
1. Single dose, 500 mg film-coated tablets, adults
2. Three times a day, 500 mg oral formulation, adults
3. Single dose, 20 mg/kg and 10 mg/kg, oral suspension, children

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Fusidic acid

EC Number:

230-256-0

EC Name:

Fusidic acid

Cas Number:

6990-06-3

Molecular formula:

C31H48O6

IUPAC Name:

2-[(1Z,2S,3aS,3bS,5aS,6S,7R,9aS,9bS,10R,11aR)-2-(acetyloxy)-7,10-dihydroxy-3a,3b,6,9a-tetramethyl-hexadecahydro-1H-cyclopenta[a]phenanthren-1-ylidene]-6-methylhept-5-enoic acid

Test material form:

solid: crystalline

Details on test material:

Details are given for each individual study

Specific details on test material used for the study:

The clinical review covers sodium fusidate orally administrated in film-coated tablets, oral formulations and oral suspensions.

Test animals

Species:

other: humans

Sex:

not specified

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: film-coated tablets, suspensions

Details on exposure:

1. Single dose, 500 mg film-coated tablets, adults
2. Three times a day, 500 mg oral formulation, adults
3. Single dose, 20 mg/kg and 10 mg/kg, oral suspension, children

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

1. Single dose, 500 mg film-coated tablets, adults: 90-95% absorbed, serum concentration exceeding 10 mg/L after 1 hour and maximum levels reaching 30 mg/L at 3 hours. Elimination half life 9-16 hours.
2. Three times a day, 500 mg oral formulation, adults: mean accumulated serum concentration of 71 mg/L
3. Single dose, 20 mg/kg and 10 mg/kg, oral suspension, children: Maximum serum concentration of 16.9 mg/L after 2.7 hours (10 mg/kg). Elimination half life 16 h and 7.4 hours, respectively.

Details on distribution in tissues:

Studies indicate that 90% of fusidic acid is reversibly bound to plasma proteins, fusidic acid distributes by diffusion into most tissues providing concentrations in various organs ranging from 20% to 90% of matching serum concentrations, and that 95% of a single dose is eliminated from serum over 24 hours via the bile.

Toxicokinetic parameters

Toxicokinetic parameters 1

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: 9-16 hours

Remarks:

adults

Toxicokinetic parameters 2

Test no.:

#1

Toxicokinetic parameters:

C(time): 10 mg/L (1 hour)

Toxicokinetic parameters 3

Test no.:

#1

Toxicokinetic parameters:

Cmax: 30 mg/L (3 hours)

Metabolite characterisation studies

Metabolites identified:

not measured

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

1. Bioavailability of fusidate in tablets in adults is approximately 91%.
3. Bioavailability of fusidic acid in oral suspension administrated to children is 22.5% (20 mg/L) and 30-40% (10 mg/L)

Applicant's summary and conclusion

Conclusions:

Approximately 90-95% of orally administrated sodium fusidate in a single dose is absorbed and maximum serum concentration levels are reached after approximately 3 hours. The studies indicate that 95% of a single dose is eliminated from serum over 24 hours via the bile.

Executive summary:

In a clinical review on sodium fusidate orally administrated in film-coated tablets, oral formulations and oral suspensions, it is indicated that 90-95% of a single dose of sodium fusidate is absorbed and maximum serum concentration levels are reached after approximately 3 hours. Bioavailability is approximately 91% in adults and lower (22.5 -40%) in children.

The elimination half life of sodium fusidate/fusidic acid in serum is 9 -16 hours. The studies indicate that 95% of a single dose is eliminated from serum over 24 hours via the bile.