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Biomedical subjects

M Schäfer-Korting

Publications and source records attributed to M Schäfer-Korting.

At least 73 records · Page 4Linked to original sources
PubMed1986

Cefodizime penetration into skin suction blister fluid following a single intravenous dose.

Cefodizime pharmacokinetics was investigated, evaluating drug concentrations in serum, skin suction blister fluid (SBF), saliva and urine in six healthy male subjects who were administered a 1-g dose intravenously. Serum levels in five subjects can be described according to a two-compartment open model; terminal half-life is 181 +/- 14 min. Volume of distribution (Vd beta) amounts to 15.3 +/- 1.61, serum clearance to 59 +/- 6 ml/min, renal clearance to 33 +/- 3 ml/min. Of the administered dose, 54% is renally excreted unchanged within 27 h. Unbound drug fraction in serum is 19.0% and in SBF 38.4%. Thus renal clearance of free cefodizime amounts to 172 ml/min, Vdss to 68.9 l (free drug). Whereas cefodizime has not been detected in saliva samples, SBF concentration 3-9 h post administration parallel serum levels, amounting to 40% of the respective serum concentration. At 9 h, unbound cefodizime concentrations in SBF amount to 1.4 +/- 0.4 micrograms/ml, this value being well above the MIC90% values of many clinically relevant bacteria.

Adult↗
PubMed1985

Human plasma and skin blister fluid levels of griseofulvin after its repeated administration.

Griseofulvin was administered orally to 6 healthy volunteers for 6 days. The subjects received 500 mg of a microsize formulation and 330 mg of an ultramicrosize formulation, according to a cross-over design. The drug was determined in plasma, suction blister fluid (SBF) and cantharides blister fluid (CBF) following the last dose. Urinary excretion of the main metabolites 6-demethylgriseofulvin (6-DMG) and its glucuronic acid conjugate was also measured. The pharmacokinetic parameters were compared with those obtained from a recent single dose experiment. On repeated administration, the bioavailability of griseofulvin was significantly lower from the microsize formulation; the urinary recovery of total 6-DMG was 33.8% versus 53.6% on administration of the ultramicrosize material. Bioavailability was reduced as compared to ingestion of a single dose. The reduction was more prominent following the microsize (36%) than the ultramicrosize (17%) formulation. Penetration into skin blister fluid was not altered as compared to the single dose experiment. Relative areas under the blister fluid-time curves amounted to 51% (SBF) and 80% (CBF) of the area under the plasma level-time curve. The concentration of unbound griseofulvin in these body fluids was identical throughout the entire dosage interval. Unbound griseofulvin levels were low in comparison with the minimum inhibitory concentrations for strains of trichophyton and microsporum.

Blister↗
PubMed1985

Human plasma and skin blister fluid levels of griseofulvin following a single oral dose.

Griseofulvin and 6-demethylgriseofulvin (6-DMG) in plasma, suction blister fluid (SBF) and cantharides blister fluid (CBF) and urinary excretion of 6-DMG, were evaluated following administration of single oral doses of an ultramicrosize and a microsize formulation of griseofulvin to 6 healthy volunteers. The bioavailability of griseofulvin was higher following the ultramicrosize formulation when 64% of the dose was recovered (via metabolites) versus 52% after the microsize preparation. Penetration into skin blister fluid was delayed as compared to plasma levels; the peak concentration in plasma was observed at 3-4 h, whereas griseofulvin in CBF increased up to 6 h. The terminal half-live was calculated from plasma levels to 9.3 h. The half-lives calculated from SBF and CBF concentrations were 9.2 and 9.8 h, respectively, (n = 5). In plasma 84% of griseofulvin was bound to proteins, predominantly to albumin; binding in SBF and CBF was 72 and 82%, respectively. 3 h after drug administration the free concentration in plasma significantly exceeded the free concentrations in SBF and CBF. Distribution equilibrium between plasma and skin blister fluid was observed after 27 h. Thus, during chronic administration, the plasma griseofulvin level should reflect its concentration in the target organ.

Administration, Oral↗
PubMed1985

Pharmacokinetics of carteolol in relation to renal function.

The plasma levels and urinary excretion of carteolol and its main metabolites 8-hydroxycarteolol and carteolol glucuronide were investigated in 6 healthy subjects and 9 patients with varying degrees of renal impairment following a single oral dose of 30 mg carteolol hydrochloride. In healthy subjects the half-life of carteolol was 7.1 h. 63% of the administered dose was recovered unchanged in urine, and in all 84% was excreted by the kidneys. The renal clearance of carteolol was 255 ml/min. In chronic renal failure (CRF) the terminal half-life was increased to a maximum of 41 h. Both the elimination rate constant and renal clearance were closely related to the creatinine clearance. In CRF the recovery of carteolol and its metabolites from urine was considerably reduced, suggesting that another pathway of drug elimination becomes relevant in renal disease. To avoid an increase in side-effects due to drug accumulation, the dosage of carteolol should be adjusted in relation to the reduction in creatinine clearance. The maintenance dose should be reduced to a half in patients with a creatinine clearance below 40 ml/min and above 10 ml/min. In those with a creatinine clearance of 10 ml/min or less, the dose should be reduced to 1/4.

Adult↗
PubMed1985

Single-dose kinetics of oral propranolol, metoprolol, atenolol, and sotalol: relation to lipophilicity.

Nine healthy volunteers received single oral doses of the following four beta-adrenergic blocking agents: propranolol (160 mg), metoprolol (100 mg), atenolol (200 mg), and sotalol (320 mg). The kinetics of each drug were determined from multiple serum concentrations measured during 24-48 h after each dose, and in vitro lipid solubility determined using the liquid chromatographic (HPLC) retention index. Oral clearance for the four drugs ranged from 40.2 ml/min/kg for propranolol down to 2.1 for sotalol. Oral clearance was highly correlated (r = 0.99) with in vitro lipid solubility, with propranolol being the most lipophilic drug and sotalol the least. Thus lipophilicity is a physicochemical property of beta-adrenergic blockers that appears to influence their intrinsic clearance after oral dosage.

Adrenergic beta-Antagonists↗
PubMed1985

Skin blister fluid--an access to the peripheral compartment. Implications of a study on the behaviour of bendroflumethiazide in rats.

Pharmacokinetics of bendroflumethiazide (bft) were investigated in blood and skin suction blister fluid (SBF) in rats dosed 10 mg/kg intravenously. Additionally tissue levels were determined. Mean volume of skin blisters amounted to 10 or 20 microliters, respectively. While blood levels were best described according to a three-compartment model (terminal half-life 152 min) bft concentrations in SBF raised to a maximum 60 min post administration and thereafter declined (half-life 143 min). There was no significant effect of blister volume on SBF level-time course. A close relation between bft concentrations in SBF and the calculated amount of drug in the deep compartment was observed (r = 0.987). Plasma protein binding of bft was 84% while binding to SBF amounted to 76%. The drug is evenly distributed between plasma and erythrocytes. Therefore concentrations of unbound drug in SBF exceed those in plasma during the terminal phase. The determination of tissue levels showed bft concentrations in liver, kidney, lung and heart to follow blood levels whereas the pharmacokinetic behaviour of skin and muscle is rather close to that of the deep compartment. The results suggest the determination of skin blister fluid levels to be valuable if a drug acts from the tissue compartment then SBF being closer to the biophase than blood.

Albumins↗
PubMed1984

UD-CG 115--a cardiotonic pyridazinone which elevates cyclic AMP and prolongs the action potential in guinea-pig papillary muscle.

The mechanism of the positive inotropic effect of a benzimidazole-pyridazinone, UD-CG 115, was analysed in the isolated guinea-pig papillary muscle contracting isometrically at a frequency of 0.2 Hz. UD-CG 115 produced a slowly developing and poorly reversible positive inotropic effect increasing with concentration (3-300 mumol/l). The effect amounted to 30 and 74% of the maximum inotropic effect of a standard, dihydroouabain, at 34 and 300 mumol/l, respectively. Low concentrations shortened and 300 mumol/l UD-CG 115 significantly prolonged the duration of contraction. The enhancement of the maximum rate of relaxation, S2, was intermediate between those produced by isoprenaline and dihydroouabain, respectively. UD-CG 115 prolonged the duration of the transmembrane action potential (90% repol .) by up to 22% at 300 mumol/l, whereas an equieffective concentration of isoprenaline did not consistently alter action potential duration. UD-CG 115 increased Vmax and overshoot, and prolonged the duration, of slow action potentials elicited at 24 mmol/l [K]0. The inotropic potency of UD-CG 115 was not significantly changed by reserpine pretreatment of the guinea pig or by the presence of 1 mumol/l(-)-propranolol, 3 mumol/l phentolamine or 10 mumol/l cimetidine. Neither was it reduced by 10 mumol/l TTX. The inotropic effect of 100 mumol/l UD-CG 115 remained unchanged when [K]0 was elevated from 3.2 to 12.0 mmol/l. A sarcolemmal preparation of guinea- pig ventricular Na,K-ATPase was only slightly inhibited by the highest concentration of UD-CG 115.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1984

Pharmacokinetics of nadolol in healthy subjects.

In 7 healthy subjects (3 males and 4 females), the kinetics of nadolol was investigated after oral doses of 60 and 120 mg. The t 1/2 was 14.0 +/- 1.8 h. The peak plasma level was doubled on doubling the dose (from 69 +/- 15 to 132 +/- 27 ng/ml, respectively) and the urinary excretion (13.5%) rose similarly. The half-life of elimination was longer at night than in the day, probably because of the slower nocturnal flow of urine.

Adult↗
PubMed1984

Simple and reliable radioreceptor assay for beta-adrenoceptor antagonists and active metabolites in native human plasma.

A radioreceptor assay (RRA) for the assay of beta-adrenoceptor antagonists in native human plasma is described. The hydrophilic antagonist 3H-CGP 12177 was used as the radioligand. In contrast to the hydrophobic radioligand 3H-dihydroalprenolol, which was investigated in parallel, the beta-adrenoceptor binding of 3H-CGP 12177 by rat reticulocyte membranes was found not to be affected by inclusion of increasing proportions (0-66% of incubation volume) of human plasma in the assay. Thus, solvent extraction of drug and/or active metabolites was not necessary to avoid binding of the radioligand tracer to plasma added in the RRA. The assay of unprocessed samples was possible. Drug concentrations in plasma after oral administration of propranolol (240 mg) or carteolol (30 mg) to 6 healthy volunteers were measured by the RRA and in parallel by a chemical method. The results from both methods agreed when the plasma concentration kinetics of propranolol were investigated (elimination half-life:3.9 h). In contrast, plasma concentrations of carteolol were consistently higher according to the RRA after oral administration of the drug. Identical concentrations, however, were found by the RRA and chemical method using plasma samples spiked with carteolol. Plasma concentrations of carteolol detected by the chemical method decline monoexponentially (elimination half-life: 5.4 h). A similar half-life of elimination for parent drug was found by the RRA (5.9 h), but an additional term describing the appearance of an active metabolite was necessary to account for the biphasic drug elimination (elimination half-life of metabolite: 17.3 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1984

Ketoconazole concentrations in human skin blister fluid and plasma.

To investigate ketoconazole penetration into skin, a single oral dose of 200 mg was administered to six healthy subjects. Plasma and cantharides blister fluid (CBF) levels were measured for 11 to 24 hours. In suction blister fluid (SBF) ketoconazole was determined 3, 6, and 9 hours after administration. Mean peak plasma levels of ketoconazole were found at 1 hour, they amounted to 3.03 +/- 0.55 micrograms/ml (n = 5). Apparent half-life of elimination was 1.8 hours. In cantharides blister fluid maximum ketoconazole concentrations were obtained at 6 hours being 1.05 +/- 0.32 micrograms/ml and declined rather slowly (half-life 4.2 hours; n = 3). Maximum concentrations in suction blister fluid were obtained 3 hours after administration (0.914 +/- 0.123 micrograms/ml). After 9 hours ketoconazole levels had declined to 0.216 +/- 0.044 micrograms/ml (n = 3). These concentrations exceed the ketoconazole concentrations proven to be effective in vitro up to 25 fold.

Adult↗
PubMed1984

Plasma, cantharides blister fluid, and suction blister fluid levels of ceftizoxime after single intramuscular application for gonorrhea.

Following a single intramuscular application of 1 g ceftizoxime, levels of the drug were determined in plasma as well as in suction blister fluid (SBF) and cantharides blister fluid (CBF). This regimen invariably led to both high and long-lasting plasma levels: 81 +/- 16 min post dose maximum plasma levels of 17.5 +/- 3.1 micrograms/ml were reached; 6 h post dose levels of 4.6 +/- 0.4 micrograms/ml were still found, i.e., 4375 and 1150 times, respectively, the MIC90% of Neisseria gonorrhoeae. The high plasma levels were parallelled by high concentrations in SBF, with peaks amounting to 8.4 +/- 1.0 micrograms/ml. Peak concentrations in CBF ranged from 8.1 to 15.7 micrograms/ml. Thus, the pharmacokinetic behavior of ceftizoxime given as a single intramuscular injection of 1 g explained the excellent clinical results of this regimen in uncomplicated gonorrhea.

Adult↗
PubMed1983

Clinical experience with atenolol in patients with chronic liver disease.

The pharmacokinetics of atenolol were investigated following single intravenous (25 mg) and oral administration (100 mg) of atenolol in 13 patients with chronic liver disease and normal renal function and in 12 normal healthy volunteers. Four of the patients with chronic liver disease were not included in the statistical evaluation of kinetic data, since a reduction of creatinine clearance was observed during the course the study after ingestion of atenolol. A tendency to an increased distribution volume of atenolol could be observed in subjects with liver disease compared to normal volunteers. After intravenous and oral administration of atenolol, pharmacokinetic parameters such as elimination half-life, plasma clearance, and renal clearance did not differ significantly between patients with chronic liver disease and healthy volunteers. Thus, plasma half-life after intravenous dosing of atenolol was 6.0 +/- 0.46 hours in patients with hepatic disease and 5.0 +/- 0.4 hours in the controls, indicating absence of atenolol accumulation in hepatic failure. In the first days after starting beta-blocker therapy such as atenolol administration, parameters of kidney function as plasma creatinine, or possibly creatinine clearance, should be initially monitored at regular intervals, as there may be transient changes of renal function in patients with chronic liver disease, leading to delayed elimination of the drug.

Administration, Oral↗
PubMed1983

Pharmacokinetics of hydrochlorothiazide in relation to renal function.

The pharmacokinetics of hydrochlorothiazide (HCT) was investigated in 23 subjects with normal renal function or widely varying degrees of renal failure. The half-life of elimination increased from 6.4 h in subjects with normal renal function to 11.5 h in patients with mild renal impairment (endogenous creatinine clearance between 30 and 90 ml/min), and to 20.7 h in patients with an endogenous creatinine clearance below 30 ml/min. The cumulative urinary excretion and the renal HCT clearance were correspondingly reduced in patients with impaired kidney function. In normal subjects HCT was mainly excreted by tubular secretion, but as renal HCT clearance in patients with renal impairment did not differ significantly from endogenous creatinine clearance, it was concluded that the secretory mechanism is most markedly impaired. In patients with an endogenous creatinine clearance of 30 to 90 ml/min, the dosage of HCT should be reduced to 1/2 and in patients with a endogenous creatinine clearance below 30 ml/min to 1/4 of the normal daily dose to avoid dose dependant side-effects.

Adult↗
PubMed1983

Atenolol interaction with aspirin, allopurinol, and ampicillin.

Atenolol kinetics were investigated in six healthy subjects after 100 mg orally, as monotherapy a 6-day treatment began 48 hr later. After a therapy-free interval of 4 wk, the same subjects received the same dose of atenolol with 1 gm ampicillin, 500 mg aspirin, and with 300 mg allopurinol. Allopurinol and aspirin did not substantially alter the kinetics of atenolol. After a single oral dose of 100 mg atenolol combined with 1 gm ampicillin, the bioavailability of atenolol was reduced to 36 +/- 5% compared to 60 +/- 8% after monotherapy. During long-term treatment with atenolol and ampicillin the bioavailability of atenolol fell to 24% (P less than 0.01). Mean peak plasma levels were lowered from 511 +/- 59 ng/ml on monotherapy to 344 +/- 33 ng/ml after the combination with ampicillin. The area under the plasma level-time curve, mean steady-state concentration, and urinary recovery were reduced, also. Twelve hours after 100 mg atenolol and 1 gm ampicillin, exercise tachycardia was significantly higher than after atenolol alone. During the 4-wk treatment in six hypertensive patients blood pressure levels of those on atenolol alone were not different from those on the combination therapy with ampicillin.

Adult↗