Zinc di(acetate)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A scientifically defensible approach was used to conduct the study. No data on GLP.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Objective of study:

absorption

Principles of method if other than guideline:

Healthy subjects were given a single oral dose of 50 mg elemental zinc as the acetate salt under either high (pH > 5) or low (pH < 3) intragastric pH conditions.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Zinc di(acetate)

EC Number:

209-170-2

EC Name:

Zinc di(acetate)

Cas Number:

557-34-6

Molecular formula:

C2H4O2.1/2Zn

IUPAC Name:

zinc diacetate

Details on test material:

- Name of test material (as cited in study report): Zinc acetate

Radiolabelling:

no

Test animals

Species:

human

Strain:

other: not applicable

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Age at study initiation: Females: 20.4 ± 2.1 years of age; Males: 23.8 ± 4.0 years of age.

All subjects were nonsmokers, within 20% of ideal body weight, and were judged to be in good physical condition on the basis of medical history, physical examination, blood chemistry, complete blood count, and urinalysis. Subjects were asked to refrain from taking any vitamin or mineral supplement 30 days before and during the entire study. None of the subjects were on any chronic medication with the exception of oral contraceptives. The participants were asked not to take any other medication or to consume ethanol 2 days before and during each treatment phase.

During each treatment phase, the subjects consumed a eucaloric diet that had a calculated value of 18 mg of zinc per day. The Food Processor II Nutrient & Diet Analysis System software was used to calculate the diet and determine energy needs for each subject. The daily study diet consisted of a total of 720 mL of Ensure Plus, 180 g turkey, 90 g ham, 135 g white bread, 42 g mayonnaise, 30 g lettuce, and 56 g potato chips. Varying gram weights of a lemon-lime carbonated beverage and gumdrop candy were given to make eucaloric adjustments for each subject. Deionized water was consumed by the subjects during confinement in the hospital. Subjects were allowed to consume tap water at all other times during the study.

Administration / exposure

Route of administration:

oral: capsule

Vehicle:

not specified

Duration and frequency of treatment / exposure:

The study was performed in a two-way crossover, two-phase design. The washout period between treatments was at least 7 days. The two phases were: (1) zinc acetate administered to subjects pretreated with a single dose of famotidlne 40 mg oral suspension to raise the intragastric pH >= 5; (2) zinc acetate administered to subjects with an intragastric pH <= 3.
Each subject was given a single oral dose of zinc acetate.

Doses / concentrations

Remarks:

Doses / Concentrations:
Zinc acetate capsules contained 50 mg of elemental zinc.

No. of animals per sex per dose / concentration:

Ten healthy volunteers, five male and five female, participated in this study.

Control animals:

not specified

Details on dosing and sampling:

All blood samples were collected in syringes containing zinc-free heparin and immediately transferred to zinc-free tubes. The samples were centriruged at 3000 rpm for 10 minutes at 4 ºC. Plasma fractions were transferred to zinc-free tubes and stored at -20 ºC until analysis.
Urine was collected in EDTA-washed gallon containers. At the end of each 24-hour collection, the urine volume was measured and aliquots were stored in polypropylene tubes at -20 ºC until analysis.
Plasma and urinary zinc were determined by flame atomic absorption spectrophotometry (AAS). Plasma zinc was determined after diluting (1:10) the
samples in 0.5% trace element-free nitric acid. Standards were run every five samples.

Statistics:

Plasma zinc concentrations for hour 1 through hour 8 were adjusted for baseline zinc concentration by subtracting the hour 0 concentration value. When this difference was less than 0, the baseline adjusted value was set at 0. Total zinc concentration at each dose for each subject was measured by plasma zinc area under the concentration versus time curve (AUC) formed by the baseline adjusted values from hour 0 through hour 8. Plasma zinc AUC was calculated using the trapezoidal rule method as implemented in the TRAP function available in the BMDP statistical software package (BMDP statistical software manual to accompany the 1990 software release).
Repeated measures analysis of variance (ANOVA) was used for both plasma concentration and urinary content to test the null hypothesis that mean zinc levels for plasma or urine were the same for all treatment groups. The alternative hypothesis is that at least one group was different from the others. Program 2V in BMDP was used for the repeated measures ANOVA. BMDP was run on a VAX 4000-200 computer.

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

524 µg/h/dL (low intragastric pH)

Main ADME results 2

Type:

absorption

Results:

378 µg/h/dL (high intragastric pH)

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Absorption is faster with low intragastric pH.

Metabolite characterisation studies

Metabolites identified:

not measured

Any other information on results incl. tables

The mean plasma zinc area under the curve for zinc acetate at low pH and at high pH were 524 and 378 µg/h/dL, respectively.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: Absorption is faster with low intragastric pH.
The mean plasma zinc area under the curve for zinc acetate at low pH and at high pH were 524 and 378 µg/h/dL, respectively.

Executive summary:

Healthy subjects were given a single oral dose of 50 mg elemental zinc as the acetate salt under either high (pH > 5) or low (pH < 3) intragastric pH conditions.

The mean plasma zinc area under the curve for zinc acetate at low pH and at high pH were 524 and 378 µg/h/dL, respectively. Absorption is faster with low intragastric pH.