The pharmacokinetics of orally administered S-carboxymethyl-l-cysteine in the dog,calf and sheep

The aim of this study was to investigate the feasibility of employing S-carboxymethyl-l-cysteine as a treatment of chronic obstructive pulmonary disease in dogs. To this end the pharmacokinetic parameters of orally administered S-carboxymethyl-l-cysteine were determined in the dog, cow and sheep. Six healthy beagle dogs, six endogenous Greek sheep and four Holstein Fresian calves were orally dosed with 10 mg/kg body weight of S-carboxymethyl-l-cysteine. No significant differences in T_max and T_1/2 were reported between the species. However, significantly higher AUC_(0–last), 21.56 ± 6.67 μg h ml^?1 and AUC_(0–∞), 21.63 ± 6.68 μg h ml^?1 were seen in the dogs compared to the sheep and calves. The calculated V_D was significantly higher in the sheep (10.4 ± 2.7 L kg^?1) and the calves (3.8 ± 0.7 L kg^?1) compared to the dogs (1.0 ± 0.6 L kg^?1). The rank order of increasing C_L was sheep (3.4 ± 2.7 L h^?1 kg^?1) > calves (2.7 ± 0.4 L h^?1 kg^?1) > dogs (0.5 ± 0.2 L h^?1 kg^?1). The result for the dogs was significantly lower that the calculated C_L for the sheep and calves.All these results indicate that the oral administration of S-carboxymethyl-l-cysteine may be useful during the therapeutic management of chronic obstructive pulmonary disease in dogs.     

Pilot toxicokinetic study and absolute oral bioavailability of the Fusarium mycotoxin enniatin B1 in pigs

The aim of present study was to reveal the toxicokinetic properties and absolute oral bioavailability of enniatin B1 in pigs. Five pigs were administered this Fusarium mycotoxin per os and intravenously in a two-way cross-over design. The toxicokinetic profile fitted a two-compartmental model. Enniatin B1 is rapidly absorbed after oral administration (T_1/2a = 0.15 h, T_max = 0.24 h) and rapidly distributed and eliminated as well (T_1/2elα = 0.15 h; T_1/2elβ = 1.57 h). The absolute oral bioavailability is high (90.9%), indicating a clear systemic exposure. After intravenous administration, the mycotoxin is distributed and eliminated rapidly (T_1/2elα = 0.15 h; T_1/2elβ = 1.13 h), in accordance with oral administration.     

Sulfur mustard causes oxidants/antioxidants imbalance through the overexpression of free radical producing-related genes in human mustard lungs

The aim of this study is to analyze oxidative stress (OS) and changes in expression of reactive oxygen species (ROS) producing-related genes in mustard lungs. Human lung biopsies provided from controls (n = 5) and sulfur mustard (SM)-exposed patients (n = 6). Changes in expression of dual oxidases (DUOXs), aldehyde oxidase 1 (AOX1), thyroid peroxidase (TPO), myeloperoxidase (MPO) and eosinophil Peroxidase (EPO) were measured using RT² Profiler™ PCR Array. OS was evaluated by determining bronchoalveolar lavage fluids (BALF) levels of total antioxidant capacity (TAC) and malondialdehyde (MDA). Higher TAC value was observed in BALF of controls compared with patients (0.138 ± 0.02683 μmol/l vs 0.0942 ± 0.01793 μmol/l), whereas a significant increase in MDA concentration was found in patients (0.486 ± 0.04615 nmol/l vs 0.6467 ± 0.05922 nmol/l). All ROS producing-related genes were overexpressed in the order AOX1> MPO> DUOX2> DUOX1> TPO> EPO. Upregulation of these genes may be a reason for overproduction of ROS, oxidants/antioxidants imbalance, OS and respiratory failures in mustard lungs.     

Alteration of pharmacokinetics of proguanil in healthy volunteers following concurrent administration of efavirenz

Efavirenz and proguanil are likely to be administered concurrently for the treatment of patients with HIV and malaria. The metabolism of proguanil is mediated principally by CYP2C19 while efavirenz is known to inhibit this enzyme. This study therefore investigated the effect of efavirenz on proguanil disposition. Fifteen healthy volunteers were each given 300 mg single oral doses of proguanil alone or with the 9th dose of efavirenz (400 mg daily for 11 days) in a crossover fashion. Blood samples were collected at pre-determined time intervals and analyzed for proguanil and its major metabolite, cycloguanil, using a validated HPLC method. Co-administration of proguanil and efavirenz resulted in significant increases (p < 0.05) in C_max, T_max, AUC_T and elimination half-life (T_1/2β) of proguanil compared with values for proguanil alone [C_max: 2.55 ± 0.24 mg/l vs 3.75 ± 0.48 mg/l; T_max: 2.80 ± 0.99 h vs 4.80 ± 0.99 h; AUC_T: 45.58 ± 12.75 mg h/l vs 97.00 ± 23.33 mg h/l; T_1/2β: 16.50 ± 4.55 h vs 23.24 ± 4.08 h]. Also, efavirenz caused a pronounced decrease in the AUC(metabolite)/AUC(unchanged drug) ratio of proguanil along with a significant decrease (p < 0.05) in C_max and AUC of the metabolite.These results indicate that efavirenz significantly alters the pharmacokinetics of proguanil. These suggest that the protection against malaria by proguanil may be decreased when the drug is co-administered with efavirenz and the antimalarial efficacy is dependent on cycloguanil plasma levels.     

Study on the interaction of bioactive compound S-allyl cysteine from garlic with serum albumin

Multispectroscopic techniques were used to investigate the interaction of S-allyl cysteine (SAC) from garlic with human serum albumin (HSA). UV–Vis absorption measurements prove the formation of the HSA–SAC complex. An analysis of fluorescence spectra revealed that in the presence of SAC, the quenching mechanism of HSA is considered static. The quenching rate constant K_q, K_SV, and the binding constant K_A were estimated. According to the Van’t Hoff equation, the thermodynamic parameters enthalpy change (ΔH) and entropy change (ΔS) were calculated to be −1.00 × 10⁵ J/mol and −255 J/mol/K, respectively. These indicate that hydrogen bonds and van der Waals forces are the major forces between SAC and HSA. The changes in the secondary structure of HSA, which was induced by SAC, were determined by circular dichroism spectroscopy. Energy transfer was confirmed and the distance between donor and acceptor was calculated to be 2.83 nm.     

Toxicological effects of clofibric acid and diclofenac on plasma thyroid hormones of an Indian major carp,Cirrhinus mrigala during short and long-term exposures

In the present investigation, the toxicity of most commonly detected pharmaceuticals in the aquatic environment namely clofibric acid (CA) and diclofenac (DCF) was investigated in an Indian major carp Cirrhinus mrigala. Fingerlings of C. mrigala were exposed to different concentrations (1, 10 and 100 μg L⁻¹) of CA and DCF for a period of 96 h (short term) and 35 days (long term). The toxic effects of CA and DCF on thyroid hormones (THs) such as thyroid stimulating hormone (TSH), thyroxine (T₄) and triiodothyronine (T₃) levels were evaluated. During the short and long-term exposure period TSH level was found to be decreased at all concentrations of CA (except at the end of 14^th day in 1 and 10 μg L^−l and 21^st day in 1 μg L^−l) whereas in DCF exposed fish TSH level was found to be increased when compared to control groups. T₄ level was found to be decreased at 1 and 100 μg L^−l of CA exposure at the end of 96 h. However, T₄ level was decreased at all concentrations of CA and DCF during long-term (35 days) exposure period. Fish exposed to all concentrations of CA and DCF had lower level of T₃ in both the treatments. These results suggest that both CA and DCF drugs induced significant changes (P < 0.01 and P < 0.05) on thyroid hormonal levels of C. mrigala. The alterations of these hormonal levels can be used as potential biomarkers in monitoring of pharmaceutical drugs in aquatic organisms.     

Toxicological effects of phenol on four marine microalgae

The toxic effects of phenol on four marine microalgae (Dunaliella salina, Platymonas subcordiformis, Phaeodactylum tricornutum Bohlin, and Skeletonema costatum) were evaluated. The 96 h EC₅₀ values were 72.29, 92.97, 27.32, and 27.32 mg L⁻¹, respectively, which were lower than those values of freshwater microalgae reported in the literature. During a 96-h exposure to a sub-lethal concentration of phenol (1/2 96 h EC₅₀) with green alga (D. salina) and diatom (S. costatum), reactive oxygen species (ROS) accumulation, and chlorophyll a (Chl a) content decrease were simultaneously observed in diatom cells after 48 h treatment. On the contrary, other chlorophylls in both algae were unaffected. Under transmission electron microscopy (TEM), the phenol-induced ultrastructure alterations included disappearance, or shrinkage, of nucleolus and enlargement of vacuoles, which may result in programmed cell death (PCD). The increase in number of lipid droplets may be related to phenol detoxification. These results indicate that the sensitivity of marine microalgae to phenol was dependent on some biotic factors such as cell size, ROS production, and phenol degradation ability in algal cells.     

Optimization of mead production using Response Surface Methodology

The main aim of the present work was to optimize mead production using Response Surface Methodology. The effects of temperature (x₁: 20–30 °C) and nutrients concentration (x₂: 60–120 g/hL) on mead quality, concerning the final concentrations of glucose (Y₁), fructose (Y₂), ethanol (Y₃), glycerol (Y₄) and acetic acid (Y₅), were studied. Twelve operational conditions were tested. No delays and moods were observed during fermentations. The second order polynomial models determined produced satisfactory fittings of the experimental data with regard to glucose (R² = 0.646, p = 0.001), ethanol (R² = 0.741, p = 0.049), glycerol (R² = 0.899, p = 0.002), fructose (R² = 0.902, p = 0.033) and acetic acid (R² = 0.913, p = 0.001). The optimum extraction conditions determined in order to maximize the combined responses were 24 °C and a nutrients concentration of 0.88 g/L. The mead produced under these conditions had the following characteristics: ethanol concentration of 10.2%, acetic acid 0.54 g/L, glycerol 7.8 g/L, glucose 1.8 g/L and fructose 2.5 g/L. These values were in agreement with the predicted and were within the safe limit established for acetic acid and the recommended range for glycerol. Furthermore, the residual sugars concentration was also low, decreasing the possibility of occurring undesirable refermentations.     

Influence of experimentally induced fever on the disposition of cefpirome in buffalo calves

The influence of Escherichia coli endotoxin-induced fever on the disposition of cefpirome was investigated in five male buffalo calves following a single intravenous dose of 10 mg kg⁻¹. Blood samples were collected from 1 min to 24 h of drug administration. The drug concentration in plasma was estimated by microbiological assay using E. coli as a test organism. The disposition of cefpirome followed two-compartment open model and the drug was detected above the minimum inhibitory concentration in plasma up to 12 h. The Vd_area and AUC were 0.75 ± 0.01 L kg⁻¹ and 35.1 ± 0.46 μg ml⁻¹ h, respectively. The elimination half-life of 1.81 ± 0.009 h and Cl_B of 0.29 ± 0.004 L kg⁻¹ h⁻¹ reflected rapid elimination and body clearance of cefpirome in febrile buffalo calves. Based on the results, a satisfactory dosage regimen of cefpirome in febrile buffalo calves was calculated to be 6 mg kg⁻¹ to be repeated at 8 h intervals.     

The influence of psychiatric comorbidity on the dexamethasone/CRH test in major depression

BackgroundThe outcome of the dexamethasone/corticotropin-releasing-hormone (DEX/CRH) test in depressed patients is heterogeneous. The present study investigated whether comorbidity of anxiety or somatoform disorders might be an explaining factor for this finding.MethodsThe DEX/CRH test was administered in 36 pure major depressive outpatients, 18 major depressive outpatients with a comorbid anxiety and/or somatoform disorder, and 43 healthy controls. Patients were free of psychotropic medication. Group differences in responsivity to the DEX/CRH test were analysed.ResultsDepressive patients with comorbidity showed a significant lower cortisol response compared to pure depressive patients (p = 0.04) and controls (p = 0.003). Group differences between MDD patients with and without comorbidity in cortisol responses disappeared after adjustment for post-DEX cortisol concentrations (p = 0.34).ConclusionsAn enhanced suppression of cortisol to 1.5 mg DEX is present in a subgroup of depressed patients with psychiatric comorbidity. Distinct hypothalamic-pituitary-adrenal (HPA) axis dysfunctions are revealed when comorbidity is taken into account.     

Oxidative stress contributes to silica nanoparticle-induced cytotoxicity in human embryonic kidney cells

In order to elucidate the nanoparticle-induced cytotoxicity and its mechanism, the effects of 20 and 50 nm silica nanoparticles on cultured human embryonic kidney (HEK293) cells were investigated. Cell viability, mitochondrial function, cell morphology, reactive oxygen species (ROS), glutathione (GSH), thiobarbituric acid reactive substance (TBARS), cell cycle and apoptosis were assessed under control and silica exposed conditions. Exposure to 20 or 50 nm SiO₂ nanoparticles at dosage levels between 20 and 100 μg/ml decreased cell viability in a dose-dependent manner. Median lethal dose (LD₅₀) of 24 h exposure was 80.2 ± 6.4 and 140.3 ± 8.6 μg/ml for 20 and 50 nm SiO₂ nanoparticles, respectively. Morphological examination revealed cell shrinkage and nuclear condensation after SiO₂ nanoparticle exposure. Increase in intracellular ROS level and reduction in GSH content were also observed in SiO₂ nanoparticle-exposed HEK293 cells. Increase in the amount of TBARS suggested an elevated level of lipid peroxidation. Flow cytometric analysis showed that SiO₂ nanoparticles can cause G2/M phase arrest and apoptotic sub-G1 population increase in a dose-dependent manner. In summary, exposure to SiO₂ nanoparticles resulted in a dose-dependent cytotoxicity in cultured HEK293 cells that was associated with increased oxidative stress.     

Chemical composition,antiproliferative and antioxidant properties of lipid classes in ordinary and dark muscles from chub mackerel (Scomber japonicus)

This study investigated to compare lipid profiles in ordinary and dark muscles from chub mackerel and to examine antiproliferative and antioxidative properties of lipid classes. The average levels of neutral lipids (NL), glycolipids (GL), and phospholipids (PL) in ordinary muscle were 92.32 ± 0.19%, 5.10 ± 0.48%, and 2.58 ± 0.46%; in dark muscle were 96.88 ± 0.15%, 2.59 ± 0.36%, and 0.54 ± 0.29%, respectively. The fatty acid composition indicated that PL had a higher percentage of PUFA (especially 22:6n?3) with lower percentages of SFA and MUFA compared to NL and GL (p < 0.05). The main ion peaks of GL in ordinary and dark muscles showed that monocharged and bischarged molecular ion were presented at m/z 876.9 and 438.8, respectively. In MTT assay, inhibition of AGS and HT-29 cell proliferation was greatest with the 0.5 and 1.0 mg mL^?1 GL treatments. The GL of ordinary muscle with 0.05 mg mL^?1 concentrations markedly decreased the levels of reactive oxygen species (ROS) induced by H₂O₂ compared to the control (p < 0.05). From our results, GL might have antiproliferative and antioxidant properties based on protective effect against the production of intracellular ROS.     

Clinical Pharmacokinetics of Paclitaxel Liposome with a New Route of Administration in Human Based on the Analysis with Ultra Performance Liquid Chromatography

We investigated the clinical pharmacokinetics of paclitaxel liposome with a new route of administration, which was intrapleural infusion, in nine advanced nonsmall-cell lung cancer (NSCLC) patients with malignant pleural effusions after a single administration. Paclitaxel concentrations were measured in pleural fluid and plasma using a simple and rapid ultra performance liquid chromatography (UPLC) method following intra-and inter-day validations. In subjects, AUC_0–96h values in pleural fluid and plasma were 17831 ± 6439 μgh/mL and 778 ± 328 μgh/mL, respectively, and T_max values were initial time and 6.67 h after administration and the corresponding C_max values were 558 ± 44 μg/mL and 12.89 ± 6.86 μg/mL, respectively. The T_{1/2 IP}, CL_IP and Vd_IP values in pleural fluid were 76 ± 48 h, 0.005 ± 0.002 L/hm² and 0.53 ± 0.23 L/m², respectively. The T_1/2,_pla, CL_pla, and Vd_pla values in plasma were 68.34 ± 56.74 h, 0.184 ± 0.080 L/hm², and 17.53 ± 16.57 L/m², respectively. However, some paclitaxel concentrations from several patients in plasma could not be detected at some designed time-points. Our results might offer new opportunities to design and determine individually appropriate therapeutic dosage regimens based on a pharmacokinetic profile.     

Evaluation of liver glycogen catabolism during hypercortisolism induced by the administration of dexamethasone in rats

BackgroundThe contribution of liver glycogen catabolism to hyperglycemia and glucose intolerance induced by pharmacological hypercortisolism were investigated.MethodsFor this purpose, adult maleWistar rats that received 1.0 mg/kg dexamethasone (DEX) ip at 8:00 a.m. (DEX group) or saline (CON group) once a day for 5 consecutive days were compared.ResultsExperimental hypercortisolism was confirmed by higher (p < 0.05) glycemia, lower (p < 0.05) body weight and glucose intolerance. In the fed state, the basal glycogen catabolism and the glucagon (1 nM) and epinephrine (2 μM) induced glycogen catabolism were similar between the groups. The activation of glycogen catabolism induced by phenylephrine (2 μM) and isoproterenol (20 μM) were increased (p < 0.05) and decreased (p < 0.05), respectively, in DEX rats. Furthermore, DEX rats exhibited higher (p < 0.05) glycogen catabolism during the infusion of cAMP (3 μM). However, during the infusion of cAMP (15 μM), 6MBcAMP (3 μM) or cyanide (0.5 mM), the intensification of glycogen breakdown was similar. Thus, in general, hypercortisolism does not influence the basal glycogen catabolism and the liver responsiveness to glycogenolytic agents in the fed state. In contrast with fed state, fasted rats (DEX group) showed a more intense (p < 0.05) basal glycogen catabolism.ConclusionThe contribution of glycogen catabolism to hyperglycemia during hypercortisolism depends of the nutritional status, starting from a negligible participation in the fed state up to a significant contribution in the fasted state.     

Molecular Relaxation Behavior and Isothermal Crystallization above Glass Transition Temperature of Amorphous Hesperetin

The purpose of this paper was to investigate the relaxation behavior of amorphous hesperetin (HRN), using dielectric spectroscopy, and assessment of its crystallization kinetics above glass transition temperature (T_g). Amorphous HRN exhibited both local (β-) and global (α-) relaxations. β-Relaxation was observed below T_g, whereas α-relaxation prominently emerged above T_g. β-Relaxation was found to be of Johari–Goldstein type and was correlated with α-process by coupling model. Secondly, isothermal crystallization experiments were performed at 363 K (T_g+ 16.5 K), 373 K (T_g+ 26.5 K), and 383 K (T_g+ 36.5 K). The kinetics of crystallization, obtained from the normalized dielectric strength, was modeled using the Avrami model. Havriliak–Negami (HN) shape parameters, α_HNand α_HN.β_HN, were analyzed during the course of crystallization to understand the dynamics of amorphous phase during the emergence of crystallites. HN shape parameters indicated that long range (α-like) were motions affected to a greater extent than short range (β-like) motions during isothermal crystallization studies at all temperature conditions. The variable behavior of α-like motions at different isothermal crystallization temperatures was attributed to evolving crystallites with time and increase in electrical conductivity with temperature. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:167–178, 2014     

Investigation of PEG Crystallization in Frozen PEG-Sucrose-Water Solutions. I. Characterization of the Nonequilibrium Behavior during Freeze-Thawing

Our objective was to characterize the nonequilibrium thermal behavior of frozen aqueous solutions containing PEG and sucrose. Aqueous solutions of (i) sucrose (10%, w/v) with different concentrations of PEG (1–20%, w/v), and (ii) PEG (10%, w/v) with different concentrations of sucrose (2–20%, w/v), were cooled to ? 70°C at 5°C/min and heated to 25°C at 2°C/min in a differential scanning calorimeter. Annealing was performed at temperatures ranging from ? 50 to ? 20°C for 2 or 6 h. Similar experiments were also performed in the low-temperature stage of a powder X-ray diffractometer. A limited number of additional DSC experiments were performed wherein the samples were cooled to ? 100°C. In unannealed systems with a fixed sucrose concentration (10%, w/v), the T′_g decreased from ? 35 to ? 48°C when PEG concentration was increased from 1% to 20% (w/v). On annealing at ? 25°C, PEG crystallized. This was evident from the increase in T′_g and the appearance of a secondary melting endotherm in the DSC. Low- temperature XRD provided direct evidence of PEG crystallization. Annealing at temperatures ≤?40°C did not result in crystallization and a devitrification event was observed above the T′_g. In unannealed systems with a fixed PEG concentration (10%, w/v), the T′_g increased from ? 50 to ? 40°C when sucrose concentration was increased from 5% to 50%, w/v. As the annealing time increased (at ? 25°C), the T′_g approached that of a sucrose-water system, reflecting progressive PEG crystallization. A second glass transition at ~? 65°C was evident in unannealed systems [10%, w/v sucrose and 10 (or 20%), w/v PEG] cooled to ? 100°C. Investigation of the nonequilibrium behavior of frozen PEG-sucrose-water ternary system revealed phase separation in the freeze-concentrate. Annealing facilitated PEG crystallization.     

Effects of TiO2 nanoparticles on ROS production and growth inhibition using freshwater green algae pre-exposed to UV irradiation

This study investigated the possibility that titanium dioxide nanoparticles (nano-TiO₂) toxicity in Pseudokirchneriella subcapitata involves reactive oxygen species (ROS) production, using the dichlorodihydrofluorescein (DCF) assay. Algae were exposed to nano-TiO₂ under laboratory fluorescent lamps supplemented with UV irradiation for 3 h, with or without a UV filter. Results showed that nano-TiO₂ increased ROS production in UV-exposed cells, with or without a UV filter (LOEC values were 250 and 10 mg/L, respectively). Sublethal effects of nano-TiO₂ on UV pre-exposed algae were also examined. Toxicity studies indicated that exposure to nano-TiO₂ agglomerates decreased algal growth following 3 h pre-exposure to UV, with or without a UV filter (EC₅₀s were 8.7 and 6.3 mg/L, respectively). The present study suggests that the growth inhibitory effects of nano-TiO₂ in algae occurred at concentrations lower than those that can elevate DCF fluorescence, and that ROS generation is not directly involved with the sublethal effects of nano-TiO₂ in algae.     

Chemical composition and anticancer,antiinflammatory, antioxidant and antimalarial activities of leaves essential oil of Cedrelopsis grevei

The essential oil from Cedrelopsis grevei leaves, an aromatic and medicinal plant from Madagascar, is widely used in folk medicine. Essential oil was characterized by GC–MS and quantified by GC–FID. Sixty-four components were identified. The major constituents were: (E)-β-farnesene (27.61%), δ-cadinene (14.48%), α-copaene (7.65%) and β-elemene (6.96%). The essential oil contained a complex mixture consisting mainly sesquiterpene hydrocarbons (83.42%) and generally sesquiterpenes (98.91%). The essential oil was tested cytotoxic (on human breast cancer cells MCF-7), antimalarial (Plasmodium falciparum), antiinflammatory and antioxidant (ABTS and DPPH assays) activities. C. grevei essential oil was active against MCF-7 cell lines (IC₅₀ = 21.5 mg/L), against P. falciparum, (IC₅₀ = 17.5 mg/L) and antiinflammatory (IC₅₀ = 21.33 mg/L). The essential oil exhibited poor antioxidant activity against DPPH (IC₅₀ > 1000 mg/L) and ABTS (IC₅₀ = 110 mg/L) assays. A bibliographical review was carried out of all essential oils identified and tested with respect to antiplasmodial, anticancer and antiinflammatory activities. The aim was to establish correlations between the identified compounds and their biological activities (antiplasmodial, anticancer and antiinflammatory). According to the obtained correlations, 1,4-cadinadiene (R² = 0.61) presented a higher relationship with antimalarial activity. However, only (Z)-β-farnesene (R² = 0.73) showed a significant correlation for anticancer activity.     

Randomized response estimates for doping and illicit drug use in elite athletes

BackgroundTo date, there are estimates for the percentage of unknown cases of doping and illicit drug use in fitness sports, but not for elite sports. This can be attributed to the problem of implementing questionnaires and surveys to get reliable epidemiological estimates of deviant or illicit behaviour.MethodsAll athletes questioned were subject to doping controls as members or junior members of the national teams. In order to estimate the prevalence of doping and illicit drug abuse, the athletes were either issued an anonymous standardized questionnaire (SQ; n = 1394) or were interviewed using randomized response technique (RRT; n = 480). We used a two-sided z-test to compare the SQ and RRT results with the respective official German NADA data on the prevalence of doping.ResultsOfficial doping tests only reveal 0.81% (n = 25,437; 95% CI: 0.70–0.92%) of positive test results, while according to RRT 6.8% (n = 480; 95% CI: 2.7–10.9%) of our athletes confessed to having practiced doping (z = 2.91, p = 0.004). SQ and RRT both revealed a prevalence of about 7% for illicit drug use, but SQ failed to indicate a realistic prevalence of doping (0.20%; 95% CI: 0.02–0.74%).ConclusionsWe demonstrate for the first time that data from official doping tests underestimate the true prevalence of doping in elite sports by more than a factor of eight. Our results indicate that implementing RRT before and after anti-doping measures could be a promising method for evaluating the effectiveness of anti-doping programs.