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Additional toxicological data

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Administrative data

Endpoint:
additional toxicological information
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
9 January 1997 and 2 May 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Type of study / information:
1592U89 is a nucleoside analog that is an HIV reverse transcriptase inhibitor. This study describes a bioequivalence study of 1592U89 succinate and
hemisulfate salt forms in male cynomologous monkeys after single oral doses of 30mg(base)/kg.
Test guideline
Qualifier:
no guideline followed
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1592U89 Hemisulfate
- Molecular formula (if other than submission substance): Please see attachment 1.
- Molecular weight (if other than submission substance): Please see attachment 1.
- Structural formula attached as image file (if other than submission substance): Please see attachment 1.

- Name of test material (as cited in study report): 1592U89 Succinate
- Molecular formula (if other than submission substance): Please see attachment 2.
- Molecular weight (if other than submission substance): Please see attachment 2.
- Structural formula attached as image file (if other than submission substance): Please see attachment 2.

Results and discussion

Any other information on results incl. tables

Review of the records from the in vivo portion of the study revealed that the 1592U89 Hemisulfate was administered as a single 22 mg(base)/kg dose, rather than the 30 mg(base)/kg dose administered during the 1592U89 Succinate phase of the study.

There was no statistical difference between plasma exposure to 1592U89 in male cynomolgus monkeys from the Succinate and Hemisulfate salts forms, as measured by dose-normalized AUC(0-oo) and Cmax. Furthermore, there was no statistical difference between terminal t1/2, MRT, or Tmax for the two salt forms. Parameter estimates and variability (standard deviation) around the estimates were within expected ranges, based on historical pharmacokinetic data in cynomolgus monkeys.

Applicant's summary and conclusion

Conclusions:
There was no statistical difference between the succinate and hemisulfate salt forms in plasma exposure to 1592U89 in male cynomolgus monkeys, as measured by dose-normalized AUC(0 -oo) and Cmax. Furthermore, there was no statistical difference between terminal t1/2, MRT, or Tmax for the two salt forms. Parameter estimates and variability (standard deviation) around the estimates were within expected ranges, based on historical pharmacokinetic data in cynomolgus monkeys.
Executive summary:

Plasma concentrations of 1592U89 were determined in four male cynomolgus monkeys following single oral doses, nominally of 30mg(base)/kg of 1592U89 Succinate or 1592U89 Hemisulfate, in a randomized crossover study design.

Review of the records from the in vivo portion of the study revealed that the 1592U89 Hemisulfate was administered as a single 22mg(base)/kg dose, rather than the 30mg(base)/kg dose administered during the 1592U89 Succinate phase of the study. Therefore, exposures were compared using dose-normalized data.

There was no statistical difference between the succinate and hemisulfate salt forms in plasma exposure to 1592U89 in male cynomolgus monkeys, as measured by dose-normalized AUC(0 -oo) and Cmax. Furthermore, there was no statistical difference between terminal t1/2, MRT, or Tmax for the two salt forms. Parameter estimates and variability (standard deviation) around the estimates were within expected ranges, based on historical pharmacokinetic data in cynomolgus monkeys.