Pentaerithrityl tetranitrate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

other: Collection of data - Absorption

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference Type:

review article or handbook

Title:

Unnamed

Year:

1989

Materials and methods

Objective of study:

absorption

Test material

Test material information

Constituent 1

Reference substance name:

Pentaerithrityl tetranitrate

EC Number:

201-084-3

EC Name:

Pentaerithrityl tetranitrate

Cas Number:

78-11-5

Molecular formula:

C5H8N4O12

IUPAC Name:

3-(nitrooxy)-2,2-bis[(nitrooxy)methyl]propyl nitrate

Applicant's summary and conclusion

Executive summary:

Von Oettingen et al. (1944) administered PETN by gavage with a tenfold excess of starch in a 10% gum arabic solution (PETN concentration, 20 mg/ml) to young female albino rats. Six hours later, the entire gastrointestinal tract was isolated, and only 13% of the PETN had been absorbed.

PETN was also mixed with acetone and rubbed onto the palm of a human hand; after 1 hour, essentially all of the PETN could be recovered by washing. In contrast, PETN was absorbed after insufflation of 100 mg into the lower trachea of dogs. The resulting decrease in blood pressure peaked at about 90 minutes.

DiCarlo et al. (1967a) studied the absorption of [14C]PETN from four ligated sections of the gastrointestinal tract in female Wistar rats. Absorption from the stomach was slow, and PETN was stable in stomach acid. Absorption was rapid from the small intestine and somewhat slower from the large intestine. Although the drug remaining in the small intestine was unchanged, bacterial action appeared to cause denitration in the large intestine, resulting in the uptake of the denitrated metabolites.

Studies in humans have indicated absorption of at least 60% of an oral dose of [14C]PETN. Label appeared in the blood within 15 minutes, but only the mono-and dinitrated forms were found (Davidson et al., 1970).