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Biomedical subjects

S Nykänen

Publications and source records attributed to S Nykänen.

At least 19 recordsLinked to original sources
PubMed1999

Absorption and bioavailability of oestradiol from a gel, a patch and a tablet.

OBJECTIVES: To compare oestradiol and oestrone concentrations and bioavailability after a single dose and at a steady state during oral oestradiol valerate, transdermal oestradiol gel and transdermal oestradiol patch treatments. METHODS: Two open, randomised, cross-over studies were conducted. In the first study, 12 healthy postmenopausal women received 1.5 mg oestradiol as a transdermal gel or a 2 mg oestradiol valerate tablet daily for 14 days. In the second study, 15 postmenopausal women were treated for 18 days with 1.5 mg oestradiol gel or a transdermal patch releasing oestradiol 50 microg/24 h (replaced every 72 h). Venous blood samples for serum oestradiol and oestrone measurements with RIA were taken until 24 or 72 h after the first and last doses. RESULTS: The tablet and the transdermal gel yielded similar serum oestradiol profiles with a peak concentration 4-5 h after administration. The patch resulted in relatively stable oestradiol levels during the mid third of the wearing time whereas much lower levels were observed in the beginning and towards the end. There was no difference in the fluctuation between the peak and trough oestradiol levels between the gel (56 or 67%) and the tablet (54%) while the fluctuation was greater with the patch (89%). The bioavailability of oestradiol from the gel was 61% as compared with the tablet and 109% as compared with the patch. The gel was not bioequivalent with the tablet or the patch. CONCLUSIONS: The doses used of the transdermal gel and the patch roughly corresponded to each other with regard to the amount of oestradiol absorbed whereas the bioavailability from the tablet was significantly higher than from the gel. The lack of bioequivalence, the different serum oestradiol profiles and the large intersubject variability suggest that individual dose adjustments may be needed when changing administration form.

Administration, Cutaneous↗
PubMed1998

[Natural contraception--a real option?].

In the article, a method developed by John Billings is introduced, based on the presumption that a woman will learn to know her fertile days and the day of ovulation by observing the consistency of the cervical mucus. The method has many uses. The woman gets to know her body and its functions. The woman can avoid becoming pregnant without long periods of continence and she can get pregnant when she wants it herself. The method can also provide help in various problems of childlessness.

Adult↗
PubMed1997

Steady-state pharmacokinetics of oestradiol gel in post-menopausal women: effects of application area and washing.

OBJECTIVE: To investigate the effect of cutaneous application area on oestradiol absorption using an oestradiol gel for transdermal use. Furthermore, the effect of washing of the application site on oestradiol pharmacokinetics was studied. DESIGN: Open-label, randomised, three-way cross-over study. SETTING: A clinical pharmacokinetic research unit. SUBJECTS: Sixteen healthy postmenopausal volunteers. INTERVENTIONS: During three treatment periods, subjects were treated with 1 mg oestradiol (1.0 g Divigel/Sandrena 0.1% gel), applied on the thigh to a skin area of 200 cm2, 400 cm2, or on an area 'as large as possible'. Blood samples were drawn during steady-state (on days 14-15) immediately before application and at regular time intervals thereafter. MAIN OUTCOME MEASURES: Serum oestradiol levels were measured for determination of peak concentration (Cmax), time to peak concentration (tmax) and bioavailability using the area under the time concentration curve (AUC0-24). RESULTS: Bioavailability from a 200 cm2 area was 2-fold higher than that from the largest possible area (P < 0.05). Oestradiol peak plasma concentration from a 200 cm2 area was higher than from the two larger areas (P < 0.05), which did not differ significantly from each other. Washing of the application site 30 min after application reduced the bioavailability from both the 200 cm2 and 400 cm2 application areas (P < 0.01), but peak plasma concentration from the 200 cm2 area only (P < 0.01). Time to reach peak plasma concentrations was significantly reduced with all three application areas by washing. CONCLUSION: A higher oestradiol absorption was achieved from a smaller application area. No marked differences were observed in the pharmacokinetics between 200 cm2 and 400 cm2 application areas, which are those recommended for this oestradiol gel preparation.

Administration, Cutaneous↗
PubMed1992

Effect of food on absorption and hydrolysis of erythromycin acistrate.

Effect of food on absorption of erythromycin acistrate (2'-acetyl erythromycin stearate, Erasis; CAS 96128-89-1) was studied in 14 healthy volunteers in a randomized cross-over design. The subjects were given 400 mg erythromycin acistrate enteric coated tablets b.i.d. for 4 days. On the 1st and 4th days the tablets were taken after an overnight fast or immediately after a light or a heavy breakfast. Erythromycin (E), 2'-acetyl-erythromycin (2AE), anhydroerythromycin and anhydro-2'-acetyl-erythromycin concentrations in plasma were analyzed chemically by HPLC. After a single dose the lag time of absorption (tlag) was significantly longer after both types of breakfasts as compared to fast. The tmax of E and 2AE were also somewhat delayed by food although tmax of 2AE after a heavy breakfast only differed statistically significantly from that of the fasting state. Food significantly delayed the absorption especially in some subjects since no drug was observed during the 12-h observation period in 2 and 5 of the subjects after a light and heavy breakfast, respectively. At steady state the delaying effect of food on absorption had almost disappeared. No significant differences were observed in Cmax- or AUC0-12-values between the fasting and the fed states both after a single dose or at steady state. It is concluded, that food does not affect the mean bioavailability of erythromycin acistrate neither the mean rate of absorption but in some subjects the absorption from enteric coated tablets might be significantly delayed.

Adult↗
PubMed1991

Bioavailability of erythromycin acistrate from hard gelatin capsules containing sodium bicarbonate.

Erythromycin acistrate is a new prodrug of erythromycin. Its bioavailability from hard gelatin capsules containing the drug with or without sodium bicarbonate was studied in healthy volunteers. The plasma levels of erythromycin, anhydroerythromycin, and acetylerythromycin were measured using an HPLC method. Addition of sodium bicarbonate to the capsule markedly enhanced the plasma level of the microbiologically active substance, erythromycin, doubling the Cmax and AUC values (P less than 0.05). At the same time, the lag time in the absorption curve was shortened to one-third. No changes in the plasma levels of the inactive metabolite anhydroerythromycin were noted. It is concluded that adding sodium bicarbonate to an erythromycin acistrate formulation enhances its bioavailability.

Adult↗
PubMed1988

Fate of single oral doses of erythromycin acistrate, erythromycin stearate and pelleted erythromycin base analysed by mass-spectrometry in plasma of healthy human volunteers.

The kinetics of erythromycin acistrate (EA). a new ester prodrug of erythromycin, were studied in three comparative, randomized, cross-over studies in 29 healthy volunteers. A new mass-spectrometric method was used to assay separately erythromycin, 2'-acetyl erythromycin and their anhydro (spiroketal) forms. In Part I, the total antibiotic concentration was higher after EA than after erythromycin stearate (ES; 1.8-fold) and enterocoated pellets of erythromycin base (EB, enterocapsules; 1.4-fold). In plasma, however, only about one third of 2'-acetyl erythromycin was hydrolysed to active erythromycin. Moreover, after unprotected EA tablets, a considerable proportion of erythromycin and 2'-acetyl erythromycin was inactivated by gastric acid as reflected by high concentrations of respective anhydro (spiroketal) forms. In Part II, the unprotected (regular tablets) and acid-protected tablets (dissolution starts at pH 4.5) were compared. The protected tablet, albeit not an enterotablet, was not destroyed by gastric acid. Its absorption was slightly delayed but the bioavailability was good. In this study, the absorption of total antibiotic was 2.8-fold (unprotected tablet) and 3.9-fold (protected tablet) that after enterocapsules. In Part III, the bioavailabilities of 200 and 400 mg tablets (both acid-protected) were equal.

Administration, Oral↗
PubMed1987

Pharmacokinetics of dextromethorphan and dextrorphan: a single dose comparison of three preparations in human volunteers.

We have carried out a single-dose comparison of three different dextromethorphan cough mixtures in 10 healthy human volunteers. Dextromethorphan was administered in a single dose of 60 mg in random order. The concentrations of dextromethorphan and its main metabolite, dextrorphan, were determined from the plasma samples using high performance liquid chromatography. The concentrations of dextrorphan were 170 times higher than the concentrations of dextromethorphan. No therapeutically significant differences were detected between the three preparations tested, and there were no great differences between the pharmacokinetic profiles of dextromethorphan and dextrorphan. The three test preparations were Resilar and Redol comp. (Remeda Pharmaceutical Co., Finland), and Extuson (Ferrosan Ab, Sweden).

Adult↗
PubMed1986

Pharmacokinetics of slow-release diltiazem and its effect on atrioventricular conduction in healthy volunteers.

The pharmacokinetics and effect of a slow-release and a conventional diltiazem tablet on atrioventricular conduction were compared in a randomized cross-over study after a single dose and at steady state in 12 healthy volunteers. The time to peak concentration was significantly delayed after the slow-release as compared to the conventional tablet, both after a single dose (2.7 vs. 0.9 h) and at steady-state (1.9 vs. 0.9 h). The peak concentration was also significantly reduced. There was no marked loss in bioavailability with the slow-release formulation. The maximal fluctuations in serum diltiazem at steady-state for the slow-release tablet were markedly less than after the conventional tablet (62 vs 87%). The PQ-interval was longer after the conventional tablet as compared to the slow-release tablet (both in doses of 120 mg) after a single dose (187 vs 163 ms) and at steady-state (197 vs 174 ms). The maximal prolongation was seen 1 h after intake of the drug. Heart rate was decreased only by 6-9 beats/min, irrespective of the dose. Slow-release diltiazem appears to have many advantages over a conventional tablet.

Adult↗
PubMed1985

The pharmacokinetics of glibenclamide: a single dose comparison of four preparations in human volunteers.

The pharmacokinetic properties of two new HB 420 glibenclamide preparations, Semi-Euglucon N 1.75 mg and Daonil N 1.75 mg, and of two older HB 419 glibenclamide preparations, Semi-Euglucon 2.5 mg and Daonil 2.5 mg, were compared in a randomized cross-over study in eight healthy volunteers. The HB 420 glibenclamide preparations induced peak plasma glibenclamide concentrations up to about 90 ng/ml at 1.3 to 1.4 hours after ingestion. Administration of the HB 419 preparations induced significantly lower peak plasma glibenclamide concentrations at 1.8 to 2.3 hours after ingestion. Glibenclamide was absorbed and eliminated more rapidly after administration of both HB 420 preparations than after administration of the HB 419 preparations. The mean elimination half-life of glibenclamide was 1.3 +/- 0.1 hours in the case of both HB 420 preparations and 2.0 to 2.5 +/- 0.2 hours in the case of HB 419 preparations. Although the HB 420 preparations contained lower doses of glibenclamide than the HB 419 preparations, the AUC values after administration of the former were similar to the AUC value obtained after administration of one of the HB 419 preparations, indicating improved absorption of glibenclamide from the newly developed preparations. However, the other HB 419 preparation was associated with the greatest AUC value of all, suggesting that glibenclamide was absorbed from this preparation almost as completely as from the HB 420 preparations.

Adult↗