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Biomedical subjects

M Schäfer-Korting

Publications and source records attributed to M Schäfer-Korting.

At least 55 records · Page 3Linked to original sources
PubMed1992

Is tinea unguium still widely incurable? A review three decades after the introduction of griseofulvin.

BACKGROUND: Tinea unguium, especially of the feet, for ages has been looked on as an incurable disease. Today, therapeutic outcome is still controversial. To evaluate the present state of antifungal therapy of dermatophytoses of the nails, a survey of the pertinent literature has been performed. OBSERVATIONS: The introduction of griseofulvin three decades ago was first considered a major breakthrough. Today, however, conventional griseofulvin treatment regimens must be called disappointing in terms of clinical and microbiological cure to be achieved. Cure rates of 40% to 100% have been reported for fingernail infections, but only 3% to 38% for toenail tinea. Microbiological cure rates look only slightly better. Limited experience suggests that additional measures such as surgical nail avulsion or topical antifungal treatment might improve therapeutic outcome. Toenail avulsion increases cure rates to 47% to 82%. The lack of an adequate follow up, however, makes all statements questionable. CONCLUSIONS: Results are only limited with respect to newly developed oral antifungal agents. Whereas ketoconazole treatment had to be omitted due to its hepatotoxic effect, its congener, intraconazole, is under investigation. High cure rates have been obtained in a preliminary study with oral terbinafine, 0.25 g/d, for 12 months, which have cleared toenail tinea in 15 of 17 patients. The value of topical treatment alone has not yet been definitely established. The application of a topical azole (bifonazole) in combination with chemical nail avulsion, using urea paste under occlusion, has resulted in negative cultures in 62% of the patients 3 months after the end of treatment.

Administration, Oral↗
PubMed1991

Topical liposome drugs to come: what the patent literature tells us. A review.

Drug-containing liposomes for topical use in dermatology have been devised during the last 10 years. Most recently the clinical superiority to a conventional gel of a topical glucocorticosteroid liposome preparation for eczema has been demonstrated. To get more insight from what may be expected from future liposome preparations for topical treatment, the pertinent patent literature has been reviewed.

Administration, Cutaneous↗
PubMed1991

Influence of albumin on itraconazole and ketoconazole antifungal activity: results of a dynamic in vitro study.

The relevance of intense protein binding to the antifungal activity of azole compounds is still a matter of debate. The influence of albumin on the antimicrobial activity of ketoconazole and itraconazole, which exhibit very strong plasma protein binding (99 and 99.8%), was evaluated in vitro. Candida albicans was exposed to continuously changing azole concentrations corresponding to drug levels in serum following an oral dose of 200 mg. Total as well as free drug levels in serum were simulated. The incubation medium was free of proteins or contained 4% human serum albumin. Itraconazole levels reflecting free drug concentrations in humans did not reduce the growth rate of C. albicans, as compared with controls (difference in the log CFU per milliliter at 12 h, 0.03 +/- 0.09), whereas total drug levels were as active in the presence of 4% albumin (mean difference, -0.61) as in its absence (-0.75). The same was true for ketoconazole, except that free drug levels were also active (-1.21 versus -1.39 for total drug levels). This result was due to the higher ketoconazole levels in humans. Thus, in terms of routine susceptibility testing, in vitro total drug levels can be considered relevant.

Antifungal Agents↗
PubMed1990

Liposome encapsulation improves efficacy of betamethasone dipropionate in atopic eczema but not in psoriasis vulgaris.

The effect of a liposomal preparation of beta-methasone dipropionate (0.039%, BDP) has been compared to that of a commercial propylene glycol-gel containing 0.064% BDP in a double-blind, randomized, paired trial lasting 14 d in 10 patients with atopic eczema and 10 patients with psoriasis vulgaris. In eczema, the liposome preparation tended to reduce erythema and scaling more than the conventional gel, the difference in the latter parameter being significant on Day 7. There was greater improvement of psoriasis on the side treated with the reference gel. Hence, liposome encapsulation of BDP may increase the antiinflammatory action but not the antiproliferative effect. Since inhibition of mitotic activity is linked to the atrophogenicity of topical corticosteroids, the results suggest that liposome encapsulation may improve the benefit-risk ratio in eczema.

Adult↗
PubMed1990

Skin tissue fluid levels of cefotiam in healthy man following oral cefotiam hexetil.

Cefotiam hexetil is a pro-drug of cefotiam available for oral administration. To evaluate cefotiam concentrations at the active site in skin and soft-tissue infections, drug levels in skin suction blister fluid (SBF), cantharides blister fluid (CBF) and serum were determined. Six healthy subjects received oral cefotiam 400 mg as cefotiam hexetil. On an other day 200 mg was injected intravenously. Following the oral dose, the bioavailability of cefotiam was 45.5%, and the maximum concentration in serum of 2.6 mg.l-1 was obtained at 2.1 h. Peak concentrations in both types of blister fluid (0.9 mg.l-1) were significantly lower than after the iv dose (SBF 1.4 mg.l-1, CBF 1.5 mg.l-1), and the peak levels occurred later (3.3 versus 1.5 h in CBF). Despite the delay, the extent of penetration was about 100% following either mode of administration (SBF, iv dose 112%, oral dose 117%). The cefotiam level in skin blister fluids declined significantly more slowly than the serum level. Following the oral dose, the mean terminal half life was serum 0.8 h, SBF 2.6 h and CBF 4.6 h. Cefotiam concentrations in the blister fluids were close to the MIC90 of Staphylococcus aureus, S. epidermis and H. influenzae and exceeded the MIC90 of Streptococci, E. coli and Proteus mirabilis. Thus, the oral administration of cefotiam 400 mg t.i.d. should be curative in the majority of bacterial infections of the skin and soft-tissues.

Administration, Oral↗
PubMed1990

Levels of itraconazole in skin blister fluid after a single oral dose and during repetitive administration.

Oral itraconazole is effective in the treatment of mycoses. To measure its concentrations in the tissue, levels of total and non-protein-bound itraconazole were determined in serum, suction-induced blister fluid, and cantharides-induced blister fluid. Six healthy subjects received 200 mg as a single dose, followed by 100 mg/day for 10 days. Itraconazole binding in suction-induced blister fluid (99.54%) and cantharides-induced blister fluid (99.77%) was calculated from plasma protein binding (99.8%). The single-dose study showed the drug levels in blister fluid to increase more slowly than those in serum. The terminal half-life of itraconazole in serum was 22.5 +/- 3.2 hours. Suction- and cantharides-induced blister fluid levels declined in parallel. After the final dose, itraconazole penetration into cantharides-induced blister fluid was only 70%. Moreover, trough levels of unbound itraconazole in suction- and cantharides-induced blister fluid were 0.239 +/- 0.115 and 0.334 +/- 0.101 ng/ml and thus were significantly lower than free itraconazole levels in serum (0.422 +/- 0.125 ng/ml). Thus a distribution equilibrium between serum and blister fluids was not obtained. Free drug concentrations in suction- and cantharides-induced blister fluid were far lower than the minimal inhibitory concentration values for Candida ssp. and dermatophytes.

Administration, Oral↗
PubMed1990

Multiple-dose pharmacokinetics of ofloxacin in serum, saliva, and skin blister fluid of healthy volunteers.

The pharmacokinetics of ofloxacin were determined in six healthy volunteers after oral administration of 200 mg twice daily for 3.5 days. To study the pharmacokinetic behavior at the target site in bacterial infection of the skin, drug concentrations were determined in suction blister fluid (SBF) and cantharides blister fluid (CBF), as well as in serum and saliva. Ofloxacin was measured by a high-performance liquid chromatographic assay. Ofloxacin concentrations in saliva amounted to 61 +/- 3% of levels in serum. After the final dose, ofloxacin concentrations in blister fluid and serum declined in parallel. Terminal half-lives of ofloxacin in blister fluids (SBF, 7.0 h; CBF, 6.3 h) were in accordance with serum half-life (6.6 h). Favorable penetration into the skin is suggested by high area under the concentration-time curve ratios for blister fluid and serum (CBF, 1.1; SBF, 1.3). During repeated ofloxacin intake, drug levels in SBF and CBF at 12 h amounted to 0.94 and 1.10 micrograms/ml. Thus, ofloxacin levels in the skin are well above the MIC for 90% of strains tested for, e.g., Staphylococcus aureus, Staphylococcus epidermidis, Neisseria gonorrhoeae, and various members of the family Enterobacteriaceae. This should also hold true with respect to other tissues.

Adult↗
PubMed1989

Liposome preparations: a step forward in topical drug therapy for skin disease? A review.

The production of liposomes, which was described in 1961, soon was claimed to be a useful technology for drug encapsulation. The first preparation (containing a topical antifungal agent), however, was registered only recently. Additional preparations, including some for topical therapy of skin disease, are under clinical investigation. Moreover, a variety of cosmetic products that contain liposomes is available today. In this article we review the literature on liposomes as it pertains to dermatology, including the basic principles of liposome structures and preparations, pharmacokinetics of liposomes and liposome-encapsulated drugs, and the influence on drug activity. Moreover, future applications of liposome preparations are discussed.

Absorption↗
PubMed1989

Skin blister fluid levels of ketoconazole during repetitive administration in healthy man.

Ketoconazole administered orally is used in the treatment of superficial and deep mycoses. To evaluate its active concentrations in skin tissue, serum, suction blister fluid (SBF), and cantharides blister fluid (CBF) levels of total and non-protein bound ketoconazole were determined. In general, only the free drug is considered to be the active one. Six healthy subjects received 200 mg once daily for 5 days. Total ketoconazole concentrations were determined by HPLC. The unbound fractions of ketoconazole in SBF (2.3%) and CBF (1.2%) were calculated from plasma protein binding (99.0%). Before the ultimate dose, levels of unbound ketoconazole in SBF and CBF were 0.64 +/- 0.16 and 0.70 +/- 0.25 ng/ml and were thus in accordance with free ketoconazole serum levels (0.52 +/- 0.24 ng/ml; p greater than 0.05). Furthermore, following the ultimate dose, the areas under the blister fluid level-time curves of unbound ketoconazole did not differ from the respective areas under the serum level time curves, thus distribution equilibrium between serum and skin blister fluid was obtained. Peak concentrations of free ketoconazole were (SBF) 8.6 +/- 2.9 ng/ml and (CBF) 8.9 +/- 2.3 ng/ml. Free concentrations in SBF and CBF were far below the MIC values for dermatophytes and Candida ssp. reported in the literature, leaving the concentration-effect relationship of ketoconazole still open for discussion.

Adult↗
PubMed1989

Pharmacokinetics of topical and oral antifungals.

By principle both topical and systemic antifungals are available for oral candidosis. As therapeutic results have not yet reached an optimum these modalities deserve further consideration. This especially applies to bioavailability. As candidosis in general very often is a disease confined to other tissues than blood especially to cutaneous and mucosal surfaces, it is helpful to determine the drug level found at these sites. Both total and free drug levels should be looked at. The skin blistering techniques make this possible. In vitro simulation of the level profiles of various antifungals including in particular ketoconazole found in the skin can be simulated in vitro using Grasso's model. If this is done only a very limited candidacidal effect is to be seen. Taking this fact into account as well as a limited clinical efficacy of conventional treatment protocols it looks rewarding to use conventional antifungal drugs such as ketoconazole at comparatively high doses.

Absorption↗
PubMed1989

Bactericidal effect of cefodizime against beta-lactamase-producing Neisseria gonorrhoeae in vitro. A comparison of level profiles in serum and tissue after intramuscular and intravenous administration in man.

Serum and skin suction blister fluid (SBF) level profiles as well as the profile in the hypothetical peripheral compartment in man after the single intravenous application of 1 g of cefodizime and the corresponding serum level profile after intramuscular application were simulated in the presence of beta-lactamase-producing gonococci. A rapid reduction of bacterial density was observed under each of these conditions indicating clinical efficacy of both treatment protocols in uncomplicated gonorrhoea. Considering the different level profiles in more detail both serum level profiles after intravenous and intramuscular injection turned out similarly effective: while the time needed for a 99% reduction of gonococcal density (t99%) was slightly shorter with the intravenous profile (1.45 vs. 1.68 h), the maximum relative reduction was somewhat smaller, expressed by a higher kn value (0.00024 vs. 0.00010%). The drug level profile in the hypothetical peripheral compartment proved on the whole equally effective as the serum level profiles. The suction blister fluid level profile, however, showed an inferior antigonococcal activity (kn = 0.00076%, t99% = 2.08 h). This demonstrates the value of the determination of SBF levels and their inclusion in in-vitro simulation experiments.

Cefotaxime↗
PubMed1988

The relationship between pharmacokinetics and pharmacodynamics of enoximone in healthy man.

The relationship between the pharmacokinetics and pharmacodynamics of enoximone, a new positive inotropic agent, was investigated in 6 healthy men. The volunteers received single oral and i.v. doses of 3 and 1 mg/kg, respectively, and placebo in a double-blind cross-over trial. Plasma concentrations of enoximone and its sulphoxide metabolite, effects on the corrected electromechanical systole (QS2c), the impedance cardiogram (dZ/dt)/RZ index, blood pressure and heart rate were determined over an 8-h period. Peak effects on QS2c and the (dZ/dt)/RZ index were obtained after approximately 1 h. During the first hour, the cardiac effects lagged behind the high plasma concentrations. Thereafter, the effects on QS2c were closely correlated with the plasma concentrations both of enoximone and its sulphoxide derivative (r greater than or equal to 0.90). The concentration-effect curves of both substances were parallel and were independent of the route of administration. The inotropic activity was not related to the drug level in hypothetical peripheral compartments. The results suggest that determination of plasma enoximone 1 h after administration and thereafter may be useful in assessing the haemodynamic activity of the drug. Should this observation also be present in a clinical situation, plasma enoximone measurement might be a valuable tool in management of patients suffering from heart failure.

Adult↗
PubMed1988

[In vitro bactericidal effects of ofloxacin on S. aureus].

Two Staphylococcus aureus (S. aureus) strains with differing susceptibility to penicillin G as expressed by the minimum inhibitory concentration were exposed in vitro over a period of 8 h to the continuously changing concentrations of ofloxacin achieved in human serum and cantharides blister fluid (CBF) after the single oral application of 600 mg. In both strains bacterial density was rapidly, but not totally reduced: a reduction by 99 percent took no longer than about 1 and 1.5 h resp. facing the serum level profile and about 1.5 h facing the tissue level profile. The maximum reduction of staphylococcal density in percent (kn) amounted to 0.0007 and 0.0034 and to 0.0038 and 0.0047 resp. Thus not only the serum level profiles but also the skin tissue level profiles obtainable in man proved highly effective in vitro against S. aureus irrespective of the bacterial suspectibility against penicillin G. Therefore oral ofloxacin should prove useful in staphylococcal diseases especially in so far as cutaneous tissue is involved.

Humans↗
PubMed1987

Influence of phosphodiesterase inhibition and of carbachol on inotropic effects of 8-substituted cyclic AMP analogues.

The influence of phosphodiesterase inhibitors and of carbachol on the positive inotropic effect of 8-substituted cyclic AMP analogues was studied on isometrically contracting guinea-pig papillary muscles driven at a rate of 0.2 Hz. In muscles from reserpine-pretreated animals, the phosphodiesterase inhibitors 3-isobutyl, 1-methyl xanthine (IBMX; 20 mumol/l) and papaverine (10 mumol/l) shifted the concentration-effect curves of 8-substituted cyclic AMP benzyl esters to the left, decreasing the EC50 by a factor of 10 to 25. In the presence of IBMX (5 and 20 mumol/l) or papaverine (10 mumol/l), the slopes of the concentration-effect curves of 8-substituted cyclic AMP benzyl esters became flatter. The positive inotropic effect and the increase in Vmax, overshoot and duration of slow action potentials induced by cyclic AMP analogues were not affected by carbachol (0.1-10 mumol/l). In the presence of IBMX (20 mumol/l), however, carbachol (3 mumol/l) antagonized the positive inotropic effect of 8-substituted cyclic AMP derivatives, shifting the EC50-values by a factor of 3 to the right. Cyclic AMP content determined by radioimmunoassay in individual papillary muscles was raised 1.22 and 1.63-fold in the presence of 3 and 20 mumol/l IBMX. Isoprenaline (0.1 mumol/l) induced an increase in cyclic AMP content which was not significantly different from that produced by 20 mumol/l IBMX, but in contrast to the phosphodiesterase inhibitor enhanced force of contraction by 17.7 mN as compared to 1.5 mN obtained with 20 mumol/l IBMX. The findings are consistent with a model that describes the interaction between IBMX and cyclic AMP analogues as an additive effect with only endogenously accumulated cyclic AMP (due to phosphodiesterase inhibition) being involved in the negative inotropic effect of carbachol. From the failure of carbachol to affect the positive inotropic effect of cyclic AMP analogues, it is concluded, that cyclic AMP derivatives do not act as phosphodiesterase inhibitors, and that the well-known negative inotropic effect of carbachol in the presence of cyclic AMP-elevating drugs does not occur at a step beyond cyclic AMP accumulation.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Digoxin concentrations in serum and cantharides blister fluid: correlations with cardiac response.

The relationship between the pharmacokinetics and dynamics of digoxin was investigated using a skin blistering technique that allows experimental access to tissue fluid concentrations. Eight healthy volunteers received digoxin, 1.0 mg, and placebo intravenously according to a double-blind crossover design. Drug concentrations were determined during a 72-hour period in serum, urine, and cantharides blister fluid (CBF). Digoxin levels in the hypothetic peripheral compartments were calculated from serum concentrations. Digoxin effects (total electromechanical systole [QS2c], left ventricular ejection time [LVETc], preejection period [PEPc], QTc time, heart rate, and T wave amplitude) were measured simultaneously. Peak levels in the shallow and deep compartments occurred at 12 1/2 to 20 minutes and 3 hours and the maximum concentration in CBF (2.75 +/- 0.48 ng/ml) occurred at 1 hour. Digoxin effects on QS2c, PEPc, and the ratio PEP/LVET were not related to serum concentrations but were closely related to CBF concentrations (r = 0.90). CBF concentrations were then within the range of serum digoxin concentrations usually associated with the treatment of heart failure. Thus, CBF allows experimental access to active drug concentrations after a single intravenous dose.

Adult↗
PubMed1987

Cefodizime in serum and skin blister fluid after single intravenous and intramuscular doses in healthy volunteers.

In gonorrhea therapy, cephalosporins are conventionally administered by intramuscular (i.m.) injection, which rather frequently leads to local side effects. To investigate whether the well-tolerated intravenous (i.v.) injection of cephalosporins may be of comparable gonocidal effect, levels of cefodizime, a new broad-spectrum cephalosporin, in serum and tissue fluid (suction blister and cantharides blister fluid) were determined in six healthy men. Single doses of 1 g of cefodizime were injected i.v. and i.m. according to a randomized crossover design. On i.m. injection the drug was completely bioavailable, and the peak concentration in serum was 75 +/- 8 micrograms/ml. The terminal half-life of serum levels was 2.4 h. Cefodizime concentrations in the blister fluids increased for 1.5 to 3 h after the i.v. dose and for at least 3 h on i.m. administration. The concentrations of non-protein-bound cefodizime in blister fluid already exceeded the MIC for 90% of Neisseria gonorrhoeae strains 10 min after i.v. injection and 20 to 30 min after the i.m. dose. At 6 h after each dose, active concentrations were still present in serum. The results suggest that cefodizime administered i.v. and i.m. has equivalent high cure rates in uncomplicated gonorrhea. This hypothesis should be tested further by a controlled clinical trial. If equivalent, i.v. administration excels because it is better tolerated locally.

Adult↗
PubMed1987

Can the clinical efficacy of different antibiotic dosage regimens in gonorrhoea be predicted from the gonocidal effect of the corresponding plasma level profiles simulated in vitro?

Two different gonococcal strains with equal minimum inhibitory concentrations of ceftriaxone are exposed to continuously changing concentrations of this antibiotic simulating the ones found in man after the single intramuscular application of different doses (1,000, 250, 125, 50 and 25 mg). In general the bactericidal effect on both strains decreases more or less steadily with decreasing concentrations of ceftriaxone. One of the strains, however, shows a markedly dropped bactericidal effect as soon as the dosage is further reduced from 250 mg. These findings agree with previous experience from clinical dose-range finding studies. Thus the in vitro model presented here may be valuable for predicting both the optimum dosage and the clinical efficacy of new treatment protocols for gonorrhoea.

Anti-Bacterial Agents↗