Slit2/Robo4 Signaling: Potential Role of a VEGF-Antagonist Pathway to Regulate Luteal Permeability.

Introduction The corpus luteum (CL) is dependent on luteal vascular permeability, which is controlled by human chorionic gonadotropin (hCG) via vascular endothelial growth factor (VEGF). In this study we investigated the role of a potential VEGF antagonist pathway - Slit2/Robo4 - and its influence on endothelial cell adhesion. Materials and Methods Luteinized granulosa cells (LGCs) were stimulated with hCG in the absence or presence of a VEGF inhibitor. The expression of VEGF and Slit2 were measured. Human umbilical vein endothelial cells (HUVECs) were stimulated with Slit2 or VEGF, and gene expressions of cadherin 5 (CDH5) and claudin 5 (CLDN5) were measured. Following Robo4 knockdown, CDH5, CLDN5 and endothelial permeability were measured. Results Stimulation of human LGCs with hCG significantly increased VEGF while Slit2 expression was significantly suppressed. Inhibition of VEGF action after hCG stimulation did not change Slit2 suppression. Slit2 knockdown did not affect VEGF expression. While VEGF stimulation of HUVECs significantly suppressed CDH5 and CLDN5 gene expression, stimulation of HUVECs with Slit2 resulted in a significant increase in CDH5 and CLDN5. Robo4 knockdown was done, leading to downregulation of CDH5 and CLDN5 which resulted in significantly increased permeability. Conclusions Our results indicate the existence of a VEGF-antagonist pathway in the CL that decreases vascular permeability. During the functional life of the CL the pathway is suppressed by hCG. It is possible that stimulation of this pathway could be used to treat ovarian hyperstimulation syndrome.

Outcome of smoking cessation counselling of HIV-positive persons by HIV care physicians.

OBJECTIVES: Smoking is the most prevalent modifiable risk factor for cardiovascular diseases among HIV-positive persons. We assessed the effect on smoking cessation of training HIV care physicians in counselling. METHODS: The Swiss HIV Cohort Study (SHCS) is a multicentre prospective observational database. Our single-centre intervention at the Zurich centre included a half day of standardized training for physicians in counselling and in the pharmacotherapy of smokers, and a physicians' checklist for semi-annual documentation of their counselling. Smoking status was then compared between participants at the Zurich centre and other institutions. We used marginal logistic regression models with exchangeable correlation structure and robust standard errors to estimate the odds of smoking cessation and relapse. RESULTS: Between April 2000 and December 2010, 11 056 SHCS participants had 121 238 semi-annual visits and 64 118 person-years of follow-up. The prevalence of smoking decreased from 60 to 43%. During the intervention at the Zurich centre from November 2007 to December 2009, 1689 participants in this centre had 6068 cohort visits. These participants were more likely to stop smoking [odds ratio (OR) 1.23; 95% confidence interval (CI) 1.07-1.42; P=0.004] and had fewer relapses (OR 0.75; 95% CI 0.61-0.92; P=0.007) than participants at other SHCS institutions. The effect of the intervention was stronger than the calendar time effect (OR 1.19 vs. 1.04 per year, respectively). Middle-aged participants, injecting drug users, and participants with psychiatric problems or with higher alcohol consumption were less likely to stop smoking, whereas persons with a prior cardiovascular event were more likely to stop smoking. CONCLUSIONS: An institution-wide training programme for HIV care physicians in smoking cessation counselling led to increased smoking cessation and fewer relapses.

Peripheral neuropathy as the sole initial finding in three children with infantile metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is a progressive white matter disease caused by arylsulfatase A deficiency. Demyelination in the nervous system is detected by cerebral magnetic resonance imaging (MRI) and neurophysiological studies. We present three children with infantile MLD, who had difficulties in standing and walking with absent reflexes. Protein levels in cerebral spinal fluid (CSF) were elevated and nerve conduction studies revealed slowing down of motor nerve conduction velocity. Initial cerebral MRIs showed no white matter changes. Consecutively, all three children developed clinical symptoms of neurodegenerative disease. Follow-up MRI and arylsulfatase A testing led to diagnosis of MLD. We conclude, that in young children who present with an acute/subacute demyelinating polyneuropathy, MLD is a differential diagnosis.

[Doubling of the pinna, a rare branchial arch developmental disorder]. / Doppelanlage der Ohrmuschel, eine seltene Kiemenbogen-Fehlbildung.

BACKGROUND: Auricular appendices are not unusual, but doubling of the pinna is rare. There is still a controversy if these are derivates from the first or the second branchial arch. PATIENT: The case of a 3 year old girl is described with doubling of the pinna and hemi facial atrophia. The second pinna was on third of the orthotop regular auricle. It seemed to come from the tragus anlage i. e. originating from the first otic hillock. RESULTS: The accessory pinna was resected, an aesthetic result could be achieved. CONCLUSION: Morphology and position of accessory pinnas arise again the question of the origin of the auricular hillocks. This case supports the opinion of Otto that the first hillock only belongs to the first branchial arch and the major part of the auricle is originating from the hillock 2-6 i. e. to the second branchial arch.

alpha-Tocopherol and protein kinase C inhibition enhance platelet-derived nitric oxide release.

Platelet activation is tightly regulated by products of the endothelium and platelets including nitric oxide (NO). Excess vascular oxidative stress has been associated with impaired NO release, and antioxidant status has been shown to alter endothelium-derived NO bioactivity. Although physiological levels of a-tocopherol are known to inhibit platelet function, the effect of a-tocopherol on platelet NO release is unknown. Loading platelets with physiologic levels of a-tocopherol increased platelet NO production approximately 1.5-fold (Pa-tocopherol, platelet NO release increased 50% (Pa-Tocopherol-loaded platelets also produced 74% less superoxide as compared with control (Pa-tocopherol inhibited PKC-dependent eNOS phosphorylation as determined by immunoprecipitation. Lastly, platelets isolated from NOS3-deficient mice released 80% less superoxide as compared with control animals (P=0.011), and incubation of NOS III-deficient platelets with 500 mM a-tocopherol only caused a modest additional decrease in platelet superoxide release (NS). Thus, a-tocopherol appears to enhance platelet NO release both in vitro and in vivo through antioxidant- and PKC-dependent mechanisms.

Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene.

Endothelial nitric oxide synthase (eNOS) has been identified in human platelets. Although platelet-derived nitric oxide (NO) has been shown to inhibit platelet recruitment in vitro, its role in the regulation of the hemostatic response in vivo has not been characterized. To define the role of platelet-derived NO in vivo, we studied mice that lacked a functional eNOS gene (NOSIII). Surface P-selectin expression in platelets from eNOS-deficient mice was not significantly altered; however, bleeding times were markedly decreased in eNOS-deficient versus wild-type mice (77.2+/-3 versus 133.4+/-3 seconds, P<0.00005). To determine the contribution of endothelium- versus platelet-derived NO to the bleeding time, isolated platelets from either eNOS-deficient or wild-type mice were transfused into a thrombocytopenic eNOS-deficient mouse and the bleeding time was measured. The bleeding times in mice transfused with eNOS-deficient platelets were significantly decreased compared with mice transfused with wild-type platelets (Deltableeding time, -24.6+/-9.1 and -3.4+/-5.3 seconds, respectively; P<0.04). Platelet recruitment was studied by measuring serotonin release from a second recruitable population of platelets that were added to stimulated platelets at the peak of NO production. There was 40.3+/-3.7% and 52. 0+/-2.1% serotonin release for platelets added to wild-type or eNOS-deficient platelets, respectively (P<0.05). In summary, mice that lacked eNOS had markedly decreased bleeding times even after endothelial NO production was controlled. These data suggest that the lack of platelet-derived NO alters in vivo hemostatic response by increasing platelet recruitment. Thus, these data support a role for platelet-derived NO production in the regulation of hemostasis.

Repaglinide and related hypoglycemic benzoic acid derivatives.

The structure-activity relationships in two series of hypoglycemic benzoic acid derivatives (5, 6) were investigated. Series 5 resulted from meglitinide (3) when the 2-methoxy was replaced by an alkyleneimino residue. Maximum activity was observed with the cis-3, 5-dimethyl-piperidino (5h) and the octamethyleneimino (5l) residues. Series 6 resulted from the meglitinide analogon 4 bearing an inversed amido function when the 2-methoxy, the 5-fluoro, and the alpha-methyl residue were replaced by a 2-piperidino, a 5-hydrogen, and a larger alpha-alkyl residue, respectively. An alkoxy residue ortho to the carboxy group further increased activity and duration of action in the rat. The most active racemic compound, 6al (R4 = isobutyl; R = ethoxy), turned out to be 12 times more active than the sulfonylurea (SU) glibenclamide (1). Activity was found to reside predominantly in the (S)-enantiomers. Compared with the SUs 1 and 2 (glimepiride), the most active enantiomer, (S)-6al (AG-EE 623 ZW; repaglinide; ED50 = 10 micro/kg po), is 25 and 18 times more active. Repaglinide turned out to be a useful therapeutic for type 2 diabetic patients; approval was granted recently by the FDA and the EMEA. From investigations on the pharmacophoric groups in compounds of type 5 and 6, it was concluded that in addition to the two already known-the acidic group (COOH; SO2NH) and the amidic spacer (CONH; NHCO)-the ortho residue R1 (alkyleneimino; alkoxy; oxo) must be regarded as a third one. A general pharmacophore model suitable for hypoglycemic benzoic acid derivatives, SUs, and sulfonamides is proposed (Figure 6). Furthermore, from superpositions of low-energy conformations (LECs) of 1, 2, and (S)-6al, it was concluded that a common binding conformation (LEC II; Figure 10B) may exist and that differences in binding to the SU receptor and in the mechanism of insulin release between repaglinide and the two SUs may be due to specific hydrophobic differences.

Localized spectroscopy from anatomically matched compartments: improved sensitivity and localization for cardiac 31P MRS in humans.

Several pioneering studies have demonstrated that localized 31P NMR spectroscopy of the human heart might become an important diagnostic tool in cardiology. The main limitation is due to the low sensitivity of these experiments, allowing only crude spatial resolution. We have implemented a three-dimensional version of SLOOP ("spectral localization with optimal pointspread function") on a clinical instrument. SLOOP takes advantage of all available a priori information to match the size and the shape of the sensitive volumes to the anatomical structures in the examined subject. Thus, SLOOP reduces the contamination from adjacent organs and improves the sensitivity compared to conventional techniques such as ISIS or chemical shift imaging (CSI). Initial studies were performed on six healthy volunteers at 1.5 T. The good localization properties are demonstrated by the absence of resonances from blood in the heart spectra, and by PCr-free spectra from the liver. Compared to conventional CSI, the signal-to-noise ratio of the SLOOP heart spectra was improved by approximately 30%. Taking into account the varying excitation angle in the inhomogeneous B1 field of the surface coil, the SLOOP model computes the local spin saturation at every point in space. Therefore, no global saturation correction is required in the quantitative evaluation of local spectra. In this study, we found a PCr/gamma-ATP ratio in the left ventricular wall of 1.90 +/- 0.33 (mean +/- standard deviation).

Relative bioavailability of rapidly dispersing, plain, and microencapsuled acetylsalicylic acid tablets after single dose administration.

UNLABELLED: Extent and rate of absorption of acetylsalicylic acid (ASA) from rapidly dispersing (Acesal Extra) and plain tablets (Acesal) relative to reference 1 (plain tablets, Aspirin) and from microcapsuled tablets (Micristin) relative to comparable listed tablets (reference 2, Colfarit) were assessed in 2 single-dose (0.5 g ASA), open, randomized, crossover studies with intervals of 14 days between 2 periods. Both studies were performed in 24 male and female healthy volunteers each (age 18-32 years, body weight 48-90 kg, body height 161-190 cm). ASA and its metabolite salicylic acid (SA) were measured with an HPLC method validated for ASA between 0.2 and 20 microg/ml and for SA between 0.4 and 40 microg/ml. The test tablets were considered bioequivalent with reference in extent of absorption if the 90% confidence limits of the AUC0 to infinity ratio were within the range of 0.80-1.25, and in rate of absorption if the confidence limits of the Cmax/AUC0 to infinity ratios were within 0.70-1.43. RESULTS: Geometric means and 90% confidence limits for the test/reference ratios of the comparisons Acesal vs reference 1, Acesal Extra vs reference 1 and Micristin vs reference 2 were 1.05 (0.97-1.13), 1.13 (1.05-1.22), 1.02 (0.92-1.14) for ASA AUC0 to infinity and 1.02 (0.96-1.07), 1.05 (0.99-1.11), 0.98 (0.91-1.04) for SA AUC0 to infinity, respectively. The results for Cmax/AUC of ASA were 1.16 (1.00-1.34), 1.72 (1.49-1.99), 0.83 (0.73-0.94) and of SA 1.02 (0.98-1.07), 1.07 (1.02-1.12), 0.93 (0.88-0.97). CONCLUSION: Acesal and Micristin were bioequivalent with the respective references in both extent and rate of absorption. Acesal Extra and reference 1 were bioequivalent with regard to extent only. Acesal Extra was absorbed faster.

[Severe hyponatremia as diagnostic symptom of cystic fibrosis]. / Schwere Hyponatriämie als diagnoseweisendes Symptom der cystischen Fibrose.

Report on two babies, 5 and 6 months old with severe salt depletion were admitted to our hospital with fever and gastro-enteritis. One of them failed to thrive despite normal nutrition, the other one had a protracted gastro-enteritis. Both of them had a great loss of weight, a strong dehydration and were in reduced general condition but without any signs of coma or cerebral seizures. In the differential diagnosis cystic fibrosis with chronic loss of salt exacerbated during an infection, described as "Pseudo Bartter-Syndrome" was suspected. Both babies showed increased salt concentration in the sweat and decreased chymotrypsin in the stool.

[Cerebral proton spectroscopy of people infected with the human immunodeficiency virus]. / Espectroscopia de protón en el cerebro de personas infectadas por el virus de la inmunodeficiencia humana.

BACKGROUND: This article presents a combined magnetic resonance imaging and proton spectroscopy protocol (MRI/1H-MRS) applied to study the brain of human immunodeficiency virus (HIV) infected patients. The spectroscopic results were compared with clinical and radiological parameters. PATIENTS AND METHODS: The proton spectra of 57 HIV patients and 20 control subjects were obtained from a volume of interest of 8 cm3 located in the parietooccipital region of the brain that did not include any focal lesion. The resonance areas due to N-acetyl aspartate (NAA), creatine (Cr) and choline (Cho) were obtained. The MRI exam allowed us to determine the presence of focal or diffuse lesions and the degree of atrophy. Finally, the clinical exploration included the performance of a Mini-Mental test. The NAA/Cr, NAA/Cho and Cho/Cr ratios were correlated with clinical characteristics, the result of the Mini-Mental test, the presence of lesions and the degree of atrophy. RESULTS: There were altered spectral patterns in a volume of the brain that did not contain any focal lesion. The decrease in the NAA/Cr or NAA/Cho ratios was significative when considering the presence of atrophy, the existence of signs of cognitive deficiencies or the diagnosis of AIDS-dementia complex. CONCLUSIONS: The spectral changes found in the present study suggest the existence of neuronal lesions that would be due to the HIV-infection. A combined MRI/1H-MRS study may provide a more complete information about the neurological impairment by HIV and could constitute a marker of AIDS-dementia complex.

Proton chemical shift imaging, metabolic maps, and single voxel spectroscopy of glial brain tumors.

Seventeen patients with presumed glial brain tumors were examined with proton chemical shift imaging and single voxel spectroscopy that used different echo times. Metabolite resonances were evaluated by metabolic ratios and absolutely by correcting for coil load and comparison to phantom measurements. Metabolic images were created to visualize the metabolic changes. All patients showed spectra that were different from those measured in healthy control subjects. Spectral changes were also present in normal-appearing matter (NAM) that was distant from lesions. The resonance at 3.55 ppm which is usually assigned to both myo-inositol and glycine, was the only one to allow a discrimination between healthy volunteers, astrocytoma grade II, and glioblastoma multiforme (GBM) (p < 0.02). From the different echo times used we conclude that an increase in this resonance has to be assigned to glycine rather than myo-inositol. This resonance might be used to grade human gliomas more reliably. Total creatine (Cr) decreased more drastically with malignancy than N-acetylated metabolites (NA). This led to a higher NA/Cr ratio in GBM compared to astrocytoma grade II. NA/Cr was thus pseudonormal in GBM due to a change in both nominator and denominator. This study reveals the importance of comparing magnetic resonance spectroscopy data of lesions to spectra measured in identical localizations in healthy control subjects instead of NAM and the importance of quantifying single metabolic peaks instead of creating metabolic ratios in clinical magnetic resonance spectroscopy.

Intratumoral lipids in 1H MRS in vivo in brain tumors: experience of the Siemens cooperative clinical trial.

Fifteen institutions cooperated to examine the ability of 1H MRS to characterize metabolism in vivo in 102 primary brain tumors. Spectra were acquired from single 8 cc voxels in the tumor using a spin-echo method with an echo time of 135 ms. The most intense lipid signal was that of fatty acyl methylene protons at 1.3 ppm. Intratumoral lipid signals were not detected in oligodendrogliomas, ependymomas, or meningiomas and were evident in only 1 of 6 primitive neuroectodermal tumors. Among 75 astrocytic tumors, lipid signals occurred in 16% of low grade astrocytomas (AS), 36% of anaplastic astrocytomas (AA), and 44% of glioblastomas (GB). The amount of lipids, expressed as a ratio of the intensity of the methylene signal to that of choline, increased progressively with histopathological grade (p = 0.05). Greater amounts of mobile lipids in vivo in GB, which usually contain necrosis, is in accord with the recently discovered correlation between the fraction of microscopic necrosis and the intensity of the mobile lipid signal observed ex vivo using 1H MRS. The observation of lipid signals in AA, which do not contain necrosis, suggests that mobile fatty acids may appear at a stage of metabolic insult that precedes microscopic signs of cell death, and raises the possibility of an independent correlation between 1H MRS-detectable lipids and prognosis in patients with astrocytic tumors.

Proton magnetic resonance spectroscopy in patients with glial tumors: a multicenter study.

The authors represent a cooperative group of 15 institutions that examined the feasibility of using metabolic features observed in vivo with 1H-magnetic resonance (MR) spectroscopy to characterize brain tumors of the glial type. The institutions provided blinded, centralized MR spectroscopy data processing long with independent central review of MR spectroscopy voxel placement, composition and contamination by brain, histopathological typing using current World Health Organization criteria, and clinical data. Proton 1H-MR spectroscopy was performed using a spin-echo technique to obtain spectra from 8-cc voxels in the tumor and when feasible in the contralateral brain. Eighty-six cases were assessable, 41 of which had contralateral brain spectra. Glial tumors had significantly elevated intensities of choline signals, decreased intensities of creatine signals, and decreased intensities of N-acetylaspartate compared to brain. Choline signal intensities were highest in astrocytomas and anaplastic astrocytomas, and creatine signal intensities were lowest in glioblastomas. However, whether expressed relative to brain or as intratumoral ratios, these metabolic characteristics exhibited large variations within each subtype of glial tumor. The resulting overlaps precluded diagnostic accuracy in the distinction of low-and high-grade tumors. Although the extent of contamination of the 1H-MR spectroscopy voxel by brain had a marked effect on metabolite concentrations and ratios, selection of cases with minimal contamination did not reduce these overlaps. Thus, each type and grade of tumor is a metabolically hetero-geneous group. Lactate occurred infrequently and in all grades. Mobile lipids, on the other hand, occurred in 41% of high-grade tumors with higher mean amounts found in glioblastomas. This result, coupled with the recent demonstration that intratumoral mobile lipids correlate with microscopic tumor cell necrosis, leads to the hypothesis that mobile lipids observed in vivo in 1H-MR spectroscopy may correlate independently with prognosis of individual patients.

A multicenter proton magnetic resonance spectroscopy study of neurological complications of AIDS.

Human immunodeficiency virus (HIV) infection as seen in Europe and the United States has predominantly been contracted through male homosexual sex or intravenous drug abuse. In infected subjects, the brain is frequently affected both clinically and neuropathologically. The aim of this multicenter study has been to evaluate the value of single-voxel proton magnetic resonance spectroscopy (MRS) in the assessment of the neurological complications of acquired immunodeficiency syndrome (AIDS). MRS (voxel size = 8 ml, TR/TE = 1600/135 msec) was performed in 137 HIV-1-seropositive patients and 64 healthy controls without risk factors at three clinical MR sites operating at 1.5 T. The first result of this multicenter trial is that good reproducibility of results among participating sites was found. This demonstrates the reliability and robustness of MRS in the study of in vivo brain metabolism. In HIV patients, there was no significant correlation between metabolite ratios of brain detected by MRS and CDC grouping of patients or CD4 count. In contrast, the variations of brain metabolite ratios (NA/Cr, NA/Cho, and Cho/Cr) were related to the occurrence of encephalopathy, brain atrophy, or diffuse white matter lesions. There was no significant difference in brain metabolites between male homosexual AIDS patients and male intravenous drug user AIDS patients, whatever their neurological status (neurosymptomatic or neuroasymptomatic). Thus, the mode of transmission of HIV infection does not appear to affect the cerebral changes observed in the proton spectra from AIDS patients. Because of its ease of implementation and high information content, single-voxel proton MRS is likely to play a significant role in the evaluation of HIV-related encephalopathies.

Reference tables for the intrasubject coefficient of variation in bioequivalence studies.

Bioequivalence studies are usually performed as crossover studies and, therefore, information on the intrasubject coefficient of variation is needed for sample size planning. However, this information is usually not accessible in publications on bioequivalence studies, and only the pooled inter- and intrasubject coefficient of variation for either test or reference formulation is reported. It is the purpose of the present communication to provide reference values of the intrasubject coefficient of variation for various previously investigated drugs. The presentation includes pertinent pharmacokinetic characteristics for immediate- and extended-release formulations in single- and multiple-dose crossover studies.

1H MR spectroscopy in patients with metastatic brain tumors: a multicenter study.

In a cooperative study involving six clinical MR centers, localized 1H MR spectroscopy was used to characterize untreated metastatic brain tumors (40 cases, 45 lesions). Cubic volumes (3.4 or 8 cm3) filled for more than 50% by metastatic brain tissue were examined by single-voxel double spin echo MRS, by using chemical shift selective imaging (CHESS) pulses for water suppression and TE = 135 ms. Choline (Cho), creatine (Cr) and N-acetyl aspartate (NAA) levels in brain metastases of mammary carcinoma (n = 13), lung cancer (n = 11) and melanoma (n = 10) were similar. Metastasis NAA/Cho signal intensity ratio varied between 0.00 and 1.17, compared with 2.68 +/- 0.56 (SD) in lobus occipitalis and 1.94 +/- 0.63 in corpus nuclei caudati region (P < 0.0001, both). 1H MR spectroscopy, although not suited to recognize the primary tumor of metastases, could serve as a clinical test for excluding (metastatic) tumor as cause of solitary focal brain disorders that are hard to diagnose with current imaging methods.

Lacking effect of grapefruit juice on theophylline pharmacokinetics.

Grapefruit juice inhibits the biotransformation of several drugs, including caffeine (23% clearance reduction), which is metabolized by the cytochrome P450 isoform CYP1A2. Since CYP1A2 also participates in theophylline biotransformation, a randomized change-over study on a possible interaction between grapefruit juice and theophylline was conducted. Twelve healthy young male nonsmokers were included (median 26 (range 23-30) years, weight 73 (65-85) kg). Theophylline was given as a single dose of 200 mg in solution (Euphyllin 200), diluted by 100 ml of either water or grapefruit juice (751 mg/l naringin). Subsequently, additional fractionated 0.91 of water or juice were administered until 16 hours postdose. Theophylline concentrations in plasma withdrawn up to 24 hours postdose were measured by HPLC, and its pharmacokinetics were estimated using compartment model independent methods. To compare between the 2 treatments, ANOVA based point estimates and 90% confidence intervals (given in parentheses) were calculated for the test (= grapefruit coadministration) to reference (= water coadministration) ratios (Tmax: differences). These were: Cmax 0.90 (0.81-1.00), AUC 1.02 (0.95-1.11), Cmax/AUC 0.88 (0.81-0.95), T 1/2el 1.03 (0.98-1.09), Tmax 0.15 h (-0.11h-0.41 h). Thus, no pharmacokinetic interaction between grapefruit juice and theophylline was observed. This finding is in contrast to the effect of grapefruit juice reported on caffeine metabolism and may be due to the contribution of enzymes other than CYP1A2 to primary theophylline metabolism or to differences in naringin and/or naringenin kinetics between studies.

[Pharmacokinetics of a theophylline effervescent tablet]. / Pharmakokinetik einer Theophyllin Brausetablette.

The theophylline effervescent tablet (Euphyllin quick 200) provides a new acute medication for the treatment of pulmonary obstructive lung diseases. Its pharmacokinetics were determined in 12 healthy male volunteers and compared in a single-dose crossover study to those after administration of an oral solution (Euphyllin 200 ampoule). Based on the primary pharmacokinetic characteristics for rate and extent of absorption, Cmax and AUC, both formulations were bioequivalent.