[Pharmacokinetics of carvone and menthol after administration of peppermint oil and caraway oil containing enteric formulation]. / Pharmakokinetik von Carvon und Menthol nach Gabe einer Pfefferminzöl und Kümmelöl enthaltenden magensaftresistenten Formulierung.

Enteric coating of peppermint oil/caraway oil capsules avoids subjective discomfort to the patient caused by gastroesophgeal reflux. In order to confirm bioequivalence of an enteric coated formulation containing peppermint oil and caraway oil (Enteroplant) and an immediate release formulation of both oils, the pharmacokinetics of menthol and carvone after oral administration of the two formulations were studied in a randomized, two-period crossover study in 16 healthy male volunteers. The subjects received 180 mg peppermint oil and 100 mg caraway oil, once as 2 enteric coated capsules of the fixed combination preparation Enteroplant containing 90 mg peppermint oil and 50 mg caraway oil each (test) and once in the form of 5 capsules of an immediate release formulation (reference) containing 36 mg peppermint oil and 20 mg caraway oil each. The capsules were taken with 250 ml water after a 10 h fast. Both substances were determined in plasma by GC/MS after extraction. The limit of quantification was 10 ng/ml for menthol and 0.5 ng/ml for carvone. The mean maximum plasma levels for menthol were 1196 ng/ml after administration of the test medication and 1492 ng/ml after administration of the reference medication. The bioavailability with respect to the AUC was comparable after administration of test and reference preparation, the 90% confidence interval was 97 to 105%. As expected, there were considerable differences for Tmax. After application of the enteric coated form the maximum concentration was reached significantly later (3.0 h vs. 1.7 h) compared to the immediate release capsule. Corresponding data were also calculated for carvone. After application of the test medication the maxima of 14 ng/ml for both formulations were reached later (2.5 h vs. 1.3 h). The 90% confidence interval of the AUC for carvone was 79% to 119% and therefore slightly outside the acceptable range for bioequivalence of 80% to 125%. However, this fact should not be relevant, in particular since the dosage of the enteric coated capsule lies at the upper limit of the model text and positive clinical studies, also on the therapeutic equivalence of the two formulations, are available.

Pharmacokinetics of menthol and carvone after administration of an enteric coated formulation containing peppermint oil and caraway oil.

Enteric coating of peppermint oil/caraway oil capsules avoids subjective discomfort to the patient caused by gastroesophageal reflux. In order to confirm bioequivalence of an enteric coated formulation containing peppermint oil and caraway oil (CAS 277309-55-4, Enteroplant) and an immediate release formulation of both oils, the pharmacokinetics of menthol and carvone after oral administration of the two formulations were studied in a randomized, two-period cross-over study in 16 healthy male volunteers. The subjects received 180 mg peppermint oil and 100 mg caraway oil, once as 2 enteric coated capsules of the fixed enteric coated combination preparation containing 90 mg peppermint oil (WS 1340) and 50 mg caraway oil (WS 1520) each (test) and once in the form of 5 capsules of an immediate release formulation (reference) containing 36 mg peppermint (WS 1340) oil and 20 mg caraway oil (WS 1520) each. The capsules were taken with 250 ml water after a 10 h fast. Both substances were determined in plasma by GC/MS after extraction. The limit of quantification was 10 ng/ml for menthol and 0.5 ng/ml for carvone. The mean maximum plasma levels for menthol were 1196 ng/ml after administration of the test medication and 1492 ng/ml after administration of the reference medication. The bioavailability with respect to the AUC was comparable after administration of test and reference preparation, the 90% confidence interval was 97 to 105%. As expected, there were considerable differences for Tmax. After application of the enteric coated form the maximum concentration was reached significantly later (3.0 h vs. 1.7 h) compared to the immediate release capsule. Corresponding data were also calculated for carvone. After application of the test medication the maxima of 14 ng/ml for both formulations were reached later (2.5 h vs. 1.3 h). The 90% confidence interval of the AUC for carvone was 79 to 119% and therefore slightly outside the acceptable range for bioequivalence of 80 to 125%. However, this fact should not be relevant, in particular since the dosage of the enteric coated capsule lies at the upper limit of the model text and positive clinical studies, also on the therapeutic equivalence of the two formulations, are available.

Three-dimensional cephalometry using individual skeletal laser technology models.

When planning operations on the facial skull, transversal asymmetries of the maxillo-mandibular complex cannot be adequately assessed using conventional two-dimensional (2D) x-ray cephalometry. On eight patients who presented with facial skull asymmetries, a three-dimensional (3D) laser technology model (LTM) using CT data was fabricated. Five sagittal plane points and six symmetry points were marked on the LTM, measured with the FlashPoint 3-D Digitizer and then geometrically converted, such that using the sagittal plane points, sella, basion, and nasion, a method could be developed that allowed the localization of each spatial point in the three symmetry planes. Thus one could quantitatively record a patient's specific facial skull asymmetry in all three planes and a 3D measurement became feasible. Based on the measurements, the asymmetry could be assessed with respect to the sagittal, vertical, and horizontal planes. With the 3-D LTM Digitizer measuring system, the surgeon now had precise numerical information regarding the symmetry ratios of the skull at his disposal, information that would have been difficult to evaluate solely using a model analysis. The results from this study show that our measuring system is applicable and useful for complex maxillofacial asymmetries. The planning of surgical interventions was optimized because precise numerical values regarding the degree of the asymmetry were available. With the 3-D LTM Digitizer measuring system, cephalometric analysis of complex asymmetries in the three spatial planes can be pragmatically supported.

Confocal laser scanning microscopy and scanning electron microscopy of tissue Ti-implant interfaces.

Microscopic inspection of heterogenous three-dimensional (3D) objects such as oral implants, or implants in general, is conventionally performed either on ground sections of methyl-metacrylate-embedded material, at the cellular level by histologic analysis of the peri-implant tissue by light microscopy (LM), or at the supramolecular level by transmission electron microscopy (TEM). Alternatively, the architecture of the tissue/implant interface is visualized by scanning electron microscopy (SEM). The two approaches exclude each other because of the sample preparation.We elaborate conditions for the non-invasive analysis of tissue/implant interfaces by confocal laser scanning microscopy (CLSM) in buffer, hoping to obtain a 3D view of fluorescently labeled tissue constituents at the tissue implant interface and, through subsequent SEM, of the metal surface. The use of water-immersion objectives, originally developed for high LM under physiological conditions is essential. In an exploratory approach, the tissue/Ti-interfaces of two retrieved dental implants were analyzed. One was a step-cylinder used for orthodontic anchoring and the other was an endosseous step-screw implant retrieved after infection-related loosening prior to load. The adhering tissue fragments were fluorescently triple-labeled for actin, fibronectin, and sm-alpha-actin. Optical sections for fluorescent images and for the laser reflection map were registered concomitantly. This approach allowed the labeled structures to be located on the metal surface. Subsequently, the same implants were prepared for SEM of the tissue/implant interface, and upon removal of the adhering structures, of the underlying metal surface. Thus, specific proteins can be identified and their spatial architecture as well as that of the underlying metal surface can be visualized for one and the same implant. The immediate visualization after fluorescence labeling in buffer by means of water immersion objective lenses proved most critical.

Bone condensing in the placement of endosteal palatal implants: a case report.

Bone condensing as a technique to prepare an implant site is demonstrated on a patient who was to undergo orthodontic treatment utilizing a palatal implant as an anchor. Based on the anatomic constraints of the palate and the desire to load the implant as axially as possible, adapted-instrumentation for bone condensing is presented. Bone condensing for preparation of the implant site in soft maxillary bone avoids the risk of heat generation, and palatal implants can be placed precisely with primary stability.

Pharmacokinetics of dexibuprofen administered as 200 mg and 400 mg film-coated tablets in healthy volunteers.

The pharmacokinetic properties of 2 film-coated preparations containing 200 mg and 400 mg dexibuprofen were compared in a single-dose, crossover study in 16 healthy, male volunteers. Dexibuprofen was absorbed rapidly (tmax 2.1 - 2.2 hours) reaching maximum concentrations of 12.4 microg/ml (200 mg), respectively 12.0 microg/ml (400 mg dose adjusted). For the characteristics AUC(0-12h) and AUC(0-infinity) arithmetic means of 49.2 (microg) x (h/ml)(200 mg) and 48.2 (microg) x (h/ml)(400 mg dose-adjusted), respectively 50.5 (microg) x (h/ml)(200 mg), and 49.2 (microg) x (h/ml)(400 mg) were calculated. No relevant differences for the pharmacokinetic characteristics terminal half-life, clearance, volume of distribution, and mean residence time were observed. A linear dose-relationship was shown over the investigated dose range. Mean ratios after dosage adjustment of the test preparation using the "2 one-sided t-tests" procedure were calculated. Bioequivalence was assessed for AUC(0-12h) with a mean ratio of 97.7% (90% CI: 92.4 - 103.3%), for AUC(0-infinity) with 97.1% (90% CI: 91.4 - 103.1%), and for Cmax with 97.5% (90% CI: 91.7 - 103.8%). Both dexibuprofen preparations were well tolerated. No changes in hematological and biochemical parameters were detected.

Bacterial leakage into and from prefabricated screw-retained implant-borne crowns in vitro.

A mean gap of less than 4 microm following laboratory procedures and continuous loading was demonstrated in prefabricated crowns of the Ha-Ti implant system in earlier studies. The clinical relevance of such high precision in maintaining inflammation free marginal mucosa is yet to be determined. In this present investigation, the complete assembly of Ha-Ti implants including prefabricated screw-retained crowns was tested for bacterial leakage under controlled conditions in vitro. The gaps were shown not to be a barrier for Staphylococcus aureus which were used as test bacteria. Bacterial leakage through these gaps from the environment to the interior of the assembly and vice versa was observed within 24-120 h. The main path of bacterial penetration was possibly found to be through the transversal screw hole and not through the marginal gap of the prefabricated crowns.

New trends in the 3D management of CT data in plastic and reconstructive surgery.

Introduction of computer aided tomography in 1972 provided surgeons with multiple 2D maps which they themselves had to conceptualize mentally into a third dimension. The later advent of computerized summation of these data made it possible to display a perspective view of the third dimension on a TV monitor. CT, with the further analytical refinement afforded by software processing (interactive data presentation, contour detection and summation, hypothetical 3D data construction and interactive visualization) now provides the basic information that is needed for the fabrication of an individual model. Such models can be milled from polyurethane. More recently, laser-hardened acrylic resins have proved to be a useful alternative. Both systems are described and their advantages and disadvantages in the planning and performance of plastic and reconstructive surgical procedures discussed in the light of present knowledge.

Pharmacokinetics and bioequivalence of the main metabolites of selegiline: desmethylselegiline, methamphetamine and amphetamine after oral administration of selegiline.

A bioavailability study of 2 different selegiline preparations were conducted in 20 healthy volunteers to test the bioequivalence. Almost no bioavailability study of selegiline has been published. As plasma levels of selegiline are very low and the elimination half-life is very short being about 9 minutes, therefore, a very sensitive and selective method for determining the 3 main metabolites desmethylselegiline (DMS), methamphetamine (MA) and amphetamine (A) was developed. After application of a single oral dose of 5 mg selegiline the Cmax values of DMS reached 5-6 ng/ml, of MA 6-7 ng/ml and of A about 2 ng/ml. The AUC infinity values were with DMS about 11 ng/ml x h +/- 4.5, with MA about 130 g/ml x h +/- 50 and with A about 50 ng/ml x h +/- 15. The 90% confidence interval was with logarithmic transformed AUC infinity values 92-107% with DMS, 89-107% with MA, and 84-104% with A. The logarithmic transformed Cmax values showed a 90% confidence interval of 92-127% with DMS, 91-101% with MA, and 90-103% with A. All relevant pharmacokinetic parameters showed bioequivalence with all 3 metabolites (DMS, MA, and A).