Free norethisterone as reflected by saliva concentrations of norethisterone during oral contraceptive use

Abstract

Saliva and plasma concentrations of norethisterone (NET) were determined by a radioimmunoassay in 5 healthy women and in one epileptic woman on phenytoin treatment during a 21-day cycle on an oral contraceptive containing 3 mg NET-acetate and 0.05 mg ethinyloestradiol. Plasma non-protein bound concentrations of NET were determined by equilibrium dialysis. Sex hormone binding globulin (SHBG) was measured in all samples. An excellent correlation was found between plasma total, plasma non-protein bound and saliva levels of NET. Plasma non-protein bound and saliva concentrations were in the same range throughout, indicating that saliva concentrations reflect the free fraction of NET in plasma. SHBG increased considerably in all women. A slight decrease in the ratio between total and non-protein bound concentrations was found with time, possibly reflecting a slight increase in protein binding with increasing SHBG. The woman on anticonvulsant therapy had plasma total, plasma unbound and saliva NET concentrations that were only 30 per cent of those of the healthy women. The relationship between the different fractions was similar to that found in the healthy women. The non-protein bound fraction of NET was 4\p=n-\5 per cent of the total in all women studied.It is generally accepted that the pharmacologically active concentration of any given steroid is the fraction not bound to plasma proteins. In order to study the pharmacological activity and toxicity of a hormonal drug the determination of plasma nonprotein bound concentrations thus offers a more realistic opinion than the study of the total plasma concentrations of the drug. The estimation of the plasma non-protein bound fraction of a drug is usually carried out by equilibrium dialysis of plasma after determination of the total plasma concentrations by direct methods. Studies on diffe¬ rent drugs such as digoxin, phenytoin, and theophyllamine have shown that these substances are clearly detectable in the saliva and that the saliva concentrations reflect the non-protein bound frac¬ tion (Horning et al. 1977).In this study plasma and saliva concentrations of norethisterone (NET) were determined to calcu¬ late the degree of protein binding of NET and to find whether saliva NET concentrations could be used as a direct method to estimate the biologically active fraction of NET.

Steroids in Saliva for Assessing Endocrine Function

“…The low concentrations of medroxyprogesterone acetate and norethisterone in saliva are consistent with studies indicating that synthetic steroids, like the naturally occurring hormones, are extensively bound by plasma proteins (90). They are also consistent with more recent work (91), indicating an excellent correlation in plasma free and salivary norethisterone values. Measurable amounts of norethisterone were present in small aliquots of saliva (100 jul) for 6-14 h after dosage with an appropriate preparation (norethisterone, 500 jug; ethynyl estradiol, 35 jug).…”

Correlation of oestriol levels in saliva, plasma and urine of pregnant women

“…In non-pregnant women, determination of salivary steroids is handicapped by the low concentrations (1/10 of plasma levels) in which they are present. Saliva was also found to be suitable material for therapeutic drug monitoring (Horning et al 1977;Odlind & Johansson 1981). In pregnancy, E3 was found to be present in saliva mainly in the free, unconjugated form; salivary and plasma concen¬ trations of unconjugated E3 have correlated well in matched samples (Truran et al 1982).…”