Biomedical subjects

G Jütting

Publications and source records attributed to G Jütting.

At least 19 recordsLinked to original sources

PubMed1994

Pharmacokinetics of levonorgestrel and ethinylestradiol in 14 women during three months of treatment with a tri-step combination oral contraceptive: serum protein binding of levonorgestrel and influence of treatment on free and total testosterone levels in the serum.

The pharmacokinetics of levonorgestrel (LNG) and ethinylestradiol (EE2) were determined in 14 healthy women (age 18 to 27 years) during a treatment period of three months with a tri-step combination oral contraceptive (Triquilar). Prior to this treatment period, the same women received a single administration of a coated tablet containing 0.125 mg LNG together with 0.03 mg EE2. There was a washout phase of one week between both treatments. Following single dose administration, a mean terminal half-life of 22 h was observed for LNG. The total clearance was 1.0 ml x min-1 x kg-1 and the volume of distribution was 128 l. During a treatment cycle, LNG levels in the serum accumulated by a factor of about four as compared to single dose administration. Steady-state drug levels were reached during the second half of each cycle. As compared to single dose administration, the following changes were observed for LNG at the end of treatment cycles one and three: reduced total (0.5 ml x min-1 x kg-1) and free clearance (50 ml x min-1 x kg-1) and a reduced volume of distribution (52 l). A concomitant increase in the SHBG concentrations by a factor of two as compared to pretreatment values was observed during treatment and appeared to be mainly responsible for the changes in the pharmacokinetics of LNG. Marked changes were also seen for the serum protein binding of LNG. After single dose administration, the free fraction of LNG was 1.4% and the fractions bound to SHBG and albumin were 55.0% and 43.6%, respectively. At the end of cycle one, the free fraction was only 1.0% and the fractions bound to SHBG and albumin were 69.4% and 30.0%, respectively. There was no difference in corresponding pharmacokinetic parameters and in the serum protein binding of LNG at the end of cycles one and three. On the last day of treatment cycles one and three, the AUC(0-4h) values of EE2 were 331.2 and 369.6 pg x ml-1 x h, respectively, which corresponds to an about 11-24% increase as compared to single dose administration, where an AUC(0-4h) value of 298.3 pg x ml-1 x h was found. Total and free testosterone concentrations decreased during treatment cycles one and three by about 41% and 55%, respectively, compared with the corresponding values measured prior to treatment.

Administration, Oral↗

PubMed1993

Pharmacokinetics of gestodene and ethinylestradiol in 14 women during three months of treatment with a new tri-step combination oral contraceptive: serum protein binding of gestodene and influence of treatment on free and total testosterone levels in the serum.

The pharmacokinetics of gestodene (GEST) and ethinylestradiol (EE2) were determined in 14 healthy women (age 18 to 32 years) during a treatment period of three months with a new tri-step combination oral contraceptive (Milvane). Prior to this treatment period, the same women received a single administration of a coated tablet containing 0.1 mg GEST together with 0.03 mg EE2. There was a wash-out phase of one week between both treatments. Following single dose administration, a mean terminal half-life of 18 h was observed for GEST. The total clearance was 0.9 ml x min-1 x kg-1 and the volume of distribution was 84 l. During a treatment cycle, GEST levels in the serum accumulated by a factor of 8 as compared to single dose administration. Steady-state drug levels were reached during the second half of each cycle. As compared to single dose administration, the following changes were observed for GEST at the end of treatment cycles one and three: prolonged terminal half-life (20 to 22 h), reduced total (0.16 ml x min-1 x kg-1) and free clearance (ca. 27 ml x min-1 x kg-1), reduced volume of distribution (ca. 18 l). A concomitant EE2-induced increase in the SHBG concentrations by a factor of three as compared to pretreatment values was observed during a treatment cycle and appeared to be mainly responsible for the changes in the pharmacokinetics of GEST. Marked changes were also seen for the serum protein binding of GEST. After single dose administration, the free fraction of GEST was 1.3% and the fractions bound to SHBG and albumin were 69.4% and 29.3%, respectively. At the end of cycle one, the free fraction was only 0.6% and the fractions bound to SHBG and albumin were 81.4% and 18.0%, respectively. There was no difference in corresponding pharmacokinetic parameters and in the serum protein binding of GEST at the end of cycles one and three. On the last day of treatment cycles one and three, the AUC(0-4h) values of EE2 were 299.2 and 278.1 pg x ml-1 x h, respectively, which corresponds to an about 30% increase as compared to single dose administration, where an AUC(0-4h) value of 216.1 pg x ml-1 x h was found. Total and free testosterone concentrations decreased during treatment cycles one and three by about 36% and 60%, respectively, compared with the corresponding values measured prior to treatment. The fraction of unbound testosterone thus decreased from 0.5% to 0.3% during treatment.

Adolescent↗

PubMed1993

Pharmacokinetics of cyproterone acetate and ethinylestradiol in 15 women who received a combination oral contraceptive during three treatment cycles.

The pharmacokinetics of cyproterone acetate (CPA) and ethinylestradiol (EE2) were determined in 15 healthy women (age 19 to 34 years), following single dose administration of a combination oral contraceptive, containing 2.0 mg CPA together with 0.035 mg EE2 (Diane-35R). After a wash-out period of one week, the same preparation was administered during a treatment period of three months. After single dose administration, maximum concentrations of CPA in the serum were 15.2 +/- 6.6 ng/ml. Post maximum drug levels declined biphasically with half-lives of 0.8 +/- 0.4 h and 54.0 +/- 26.0 h, respectively. The apparent clearance was calculated to be 3.6 +/- 0.9 ml x min-1 x kg-1 and the volume of distribution (Vz) was 986 +/- 4371. The free fraction of CPA was 3.5 +/- 1.9% and the fractions bound to heat labile proteins and albumin were 4.6 +/- 2.2% and 92.0 +/- 3.5%, respectively. Trough levels of CPA in the serum increased during a treatment cycle, reaching a steady-state around day 16. An about two-fold accumulation of CPA was observed, which was less than expected theoretically. SHBG concentrations in the serum increased by a factor of three during a cycle, without having any effect on the protein binding of CPA. At the end of treatment cycle three, the terminal half-life of CPA had increased to a mean value of 78.6 +/- 16.0 h and the volume of distribution to a value of 1304 +/- 427 1. The apparent clearance showed a small, although significant decrease to a value of 3.0 +/- 0.4 ml x min-1 x kg-1. The observed changes Vz and t 1/2 during the treatment period were attributed to the distribution of CPA into a deep compartment and the slow release of the drug from this compartment. The AUC(0-4h) values of EE2 following single dose administration of the combination oral contraceptive were found to be 187.5 +/- 79.7 pg x ml-1 x h. On the last day of cycles one and three, the AUC(0-4h) values were 311.2 +/- 109.3 and 304.8 +/- 121.5 pg x ml-1 x h, respectively, which corresponds to an about 60% increase as compared to single dose administration. Total and free testosterone concentrations decreased during treatment cycles one and three by about 39% and 62%, respectively, compared with the corresponding values measured prior to treatment.

Adult↗

PubMed1992

Pharmacokinetics and serum protein binding of 3-keto-desogestrel in women during three cycles of treatment with a low-dose combination oral contraceptive.

The serum concentrations of 3-keto-desogestrel have been measured in 43 women who took a low-dose oral contraceptive containing 30 micrograms ethinyl estradiol (CAS 57-63-6) together with 150 micrograms desogestrel (CAS 54024-22-5) for a period of 3 months. Basic pharmacokinetic parameters, like Cmax, tmax and AUC, as well as the serum protein binding of 3-keto-desogestrel were determined on days 1, 10 and 21 of the first and the third treatment cycle, respectively. During cycle one, Cmax, AUC(0-4h) and AUC(0-24h) values on day 1 were 1.9 +/- 0.7 ng/ml, 3.9 +/- 1.3 ng.ml-1.h and 12.4 +/- 5.7 ng.ml-1.h, respectively. These values increased to 4.7 +/- 2.0 ng/ml, 12.1 +/- 5.6 ng.ml-1.h and 47.3 +/- 26.0 ng.ml-1.h on day 21. Within cycle 3, a similar, although less steep increase was observed for these parameters and there was practically no difference in the values of corresponding parameters on day 21 of both cycles. Throughout treatment, there was a redistribution of 3-keto-desogestrel with respect to the binding proteins albumin and sex hormone binding globulin (SHBG). During cycle 1, the free fraction decreased from 1.8% on day 1 to 1.1% on day 21, and the SHBG-bound fraction increased at the same time from 40% to 62%, mainly at the expense of the albumin-bound fraction. During cycle 3, there were only minor changes as compared to cycle one. The observed changes in the serum protein binding were related to an increase in SHBG levels during the treatment period.

Adult↗

PubMed1992

Pharmacokinetics and protein binding of gestodene under treatment with a low-dose combination oral contraceptive for three months.

The serum concentrations of gestodene (CAS 60282-87-3) as well as the binding of this progestin to serum proteins were studied in 40 women who took a low-dose oral contraceptive (Femovan, Femodene) containing 30 micrograms ethinyl estradiol (CAS 57-63-6) and 75 micrograms gestodene for 3 months. On days 1, 10, and 21 of the first and the third treatment cycle, respectively, 7 blood samples were drawn before and up to 4 h after pill intake; additional samples were taken prior to morning ingestion of pill on days 2, 5, 11, 15 and 22 of these cycles. Gestodene levels were measured by means of a specific radioimmunoassay and were evaluated for Cmax, tmax, and AUC up to 4 and 24 h. Independent of the test day and the treatment cycle studied, mean maximum gestodene serum levels were found about 0.8 to 0.9 h after pill intake. During the first treatment cycle, mean values of Cmax, AUC(0-4h), and AUC(0-24h) amounted to 4.3 ng.ml-1, 9.3 ng.ml-1.h, and 27.3 ng.ml-1.h on test day 1; these values increased by 250-400% and by 300-500%, respectively, when days 10 and 21 were compared to day 1. On day 1 of the third treatment cycle, these pharmacokinetic parameters were higher by almost a factor of two as compared to the corresponding data obtained on the beginning of the first cycle whereas the increase of these values between day 1 and the subsequent test days (200-300%) was slightly lower in cycle 3 as compared to cycle 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Group comparison of serum ethinyl estradiol, SHBG and CBG levels in 83 women using two low-dose combination oral contraceptives for three months.

Serum ethinyl estradiol (EE2), sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) concentrations were studied in healthy young women randomly allocated to one of two low-dose combination oral contraceptives containing 30 micrograms EE2 and either 75 micrograms gestodene (F) or 150 micrograms desogestrel (M) per unit. There was either no (formerly non-pill users) or one (pill users) wash-out cycle before the study started with a pill-free pretreatment cycle in which the hormone status and basal SHBG and CBG levels were measured. Treatment was for three months. During treatment cycles 1 and 3, there were three test days each. Seven serum samples were obtained up to four hours and one sample 24 hours after intake of the first, tenth and the last (21st) pill. Additional samples were taken prior to morning ingestion of pills 5 and 15. For each individual and each test day, a representative serum pool has been constructed for SHBG and CBG analysis. EE2 concentrations were analyzed in all individual samples by means of a specific and sensitive RIA using anti-EE2-6 beta-CMO-BSA antiserum. Area under the curves (AUC) up to 4 and 24 hours, Cmax and tmax were evaluated and compared between the two treatment groups (n = 40 for F, n = 43 for M). SHBG and CBG concentrations were measured using commercially available immunoassay kits. Groups were large enough to detect a difference in group means of 75% of one standard deviation (alpha = 0.05, 1-beta = 0.9) of target variables, which is equivalent to 28 pg EE2/ml for Cmax, 69 pg.h.ml-1 for AUCEE2 0-4h, 257 pg.h.ml-1 for AUCEE2 0-24h, 39 nmol/l SHBG and 13.4 micrograms CBG/ml. Results clearly demonstrate that there were no differences between the two treatment groups in any of the target variables at any of the six test days distributed over a three-month period. Mean SHBG and CBG pretreatment levels of about 70 nmol/l and 37 micrograms/ml, respectively, increased to about 210 nmol/l and 88 micrograms/ml during the first treatment cycle and to about 230 nmol/l and 93 micrograms/ml during the third treatment cycle. Whereas the time of maximum EE2 serum levels did not differ significantly between test days, Cmax, AUCEE2 0-4h and AUCEE2 0-24h values increased by 30-35% or 40-50%, respectively, when test days 10 and 21 were compared to test day 1. Similar results were found for the third treatment cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1973