Biodegradation Of Pharmaceuticals Research Articles

Anaerobic biodegradation of pharmaceutical compounds coupled to dissimilatory manganese (IV) or iron (III) reduction

Pharmaceuticals in water have adverse effects on aquatic environment. Anaerobic pharmaceutical biodegradation coupled to dissimilatory manganese(Mn) (IV)- or iron(Fe) (III)-oxides reduction is potentially efficient but unexplored. In this study, batch experiments were performed using different Mn(IV) and Fe(III) species with a microbial inoculum pre-cultivated with 15 mM chemically-synthesized Mn(IV) and 10 mg L−1 metoprolol. Results show 26% caffeine and 52% naproxen are degraded with Mn(IV) as terminal electron acceptor and insignificant biodegradation for other pharmaceuticals tested. Reduction of Mn(IV) from drinking water treatment is coupled to anaerobic biodegradation of metoprolol and propranolol, resulting in removal efficiencies of 96% and 31%, respectively. The results indicate that adsorption contributes to the pharmaceutical removal during the first 10 days of incubation, while biodegradation is the main removal mechanism in the whole period. Fe(III) can also be used as electron acceptor in anaerobic pharmaceutical biodegradation. Over half of the added metoprolol is degraded with both chemically-synthesized Fe(III) and Fe(III)-citrate as terminal electron acceptors. However, this process did not occur when using Fe(III) from drinking water treatment or Fe(III)-based sorbents. This study indicates that anaerobic pharmaceutical biodegradation coupled to dissimilatory Mn(IV) or Fe(III) reduction is possible, and promising for application to cleaning wastewater treatment plant effluents.

Effects of dissolved organic matter and nitrification on biodegradation of pharmaceuticals in aerobic enrichment cultures

Natural dissolved organic matter (DOM) and nitrification can play an important role in biodegradation of pharmaceutically active compounds (PhACs) in aerobic zones of constructed wetlands (CWs). This study used an enrichment culture originating from CW sediment to study the effect of DOM and nitrification on aerobic biodegradation of seven PhACs. The enriched culture degraded caffeine (CAF), metoprolol (MET), naproxen (NAP), and ibuprofen (IBP) with a consistent biodegradability order of CAF>MET>NAP>IBP. Biodegradation of propranolol, carbamazepine, and diclofenac was insignificant (<15%). CAF biodegradation was inhibited by the easily biodegradable DOM. Conversely, DOM enhanced biodegradation of MET, NAP, and IBP, potentially by contributing more biomass capable of degrading PhACs. Nitrification enhanced biodegradation of NAP and IBP and mineralization of the PhAC mixture as well as less biodegradable DOM, which may result from co-metabolism of ammonia oxidizing bacteria or enhanced heterotrophic microbial activity under nitrification. MET biodegradation was inhibited in the presence of nitrification. DOM and nitrification effects on PhAC biodegradation in CWs gained from this study can be used in strategies to improve CW operation, namely: designing hydraulic retention times based on the biodegradability order of specific PhACs; applying DOM amendment; and introducing consistent ammonium streams to increase removal of PhACs of interest.

Modeling of Pharmaceutical Biotransformation by Enriched Nitrifying Culture under Different Metabolic Conditions

Pharmaceutical removal could be significantly enhanced through cometabolism during nitrification processes. To date, pharmaceutical biotransformation models have not considered the formation of transformation products associated with the metabolic type of microorganisms. Here we report a comprehensive model to describe and evaluate the biodegradation of pharmaceuticals and the formation of their biotransformation products by enriched nitrifying cultures. The biotransformation of parent compounds was linked to the microbial processes via cometabolism induced by ammonium-oxidizing bacteria (AOB) growth, metabolism by AOB, cometabolism by heterotrophs (HET) growth, and metabolism by HET in the model framework. The model was calibrated and validated using experimental data from pharmaceutical biodegradation experiments at realistic levels, taking two pharmaceuticals as examples, i.e., atenolol and acyclovir. Results demonstrated the good predictive performance of the established biotransformation model under different metabolic conditions, as well as the reliability of the established model in predicting different pharmaceutical biotransformations. The linear positive correlation between ammonia oxidation rate and pharmaceutical degradation rate confirmed the major role of cometabolism induced by AOB in the pharmaceutical removal. Dissolved oxygen was also revealed to be capable of regulating the pharmaceutical biotransformation cometabolically, and the substrate competition between ammonium and pharmaceuticals existed especially at high ammonium concentrations.

Sorption and biodegradation of pharmaceuticals in aerobic activated sludge system: A combined experimental and theoretical mechanistic study

Understanding removal mechanisms of emerging organic contaminants in conventional activated sludge systems is of fundamental and engineering importance. In this study, we selected six environmentally relevant pharmaceuticals as target organic contaminants, namely, metronidazole (MTZ), bezafibrate (BZF), ibuprofen (IBP), sulfamethoxazole (SMX), carbamazepine (CBZ), and ciprofloxacin (CIP) for the mechanistic investigation for their removal. We demonstrated that sorption and biodegradation were the dominant pathways for contaminant removal, while volatilization and hydrolysis were negligible. The sorption removal process varied for the selected pharmaceuticals in the batch system. Then, first-order rate model was used to fit the biodegradation kinetics, and their first-order rate constants (kbio) were ranged from 3.67 × 10−3 to 10.2 L g−1 d−1, in order of CBZ < CIP < SMX < MTZ < BZF < IBP. In order to elucidate the biodegradation mechanism, we calculated a total of twelve geometrical, electrostatic, and quantum chemical descriptors with density functional theory (DFT) approach. Then, correlation analysis was conducted to investigate kbio with these theoretical descriptors. Our results indicate that electrophilicity index (ω), a measure of electrophilic power, influences the biodegradation kinetics to the greatest extent. The ω corresponds to the process where the pharmaceutical molecule acts as an electrophile, adding electron density from a nucleophile. The combined experimental and theoretical results provide insight into the intrinsic nature of biodegradation of organic contaminants of emerging concern during conventional activated sludge treatment.

Stropharia rugosoannulata and Gymnopilus luteofolius: Promising fungal species for pharmaceutical biodegradation in contaminated water

Pharmaceuticals are environmental micropollutants that pose an emerging challenge because they are poorly eliminated in conventional wastewater treatment plants. Over the last decade, many attempts have been made to solve this problem, and wastewater fungal treatment is a promising alternative. In this study, six different ligninolytic fungi (Trametes versicolor, Ganoderma lucidum, Irpex lacteus, Stropharia rugosoannulata, Gymnopilus luteofolius and Agrocybe erebia) were studied as bioremediation candidates for the removal and degradation of six recalcitrant pharmaceutical micropollutants: Carbamazepine (CBZ), Venlafaxine (VFX), Iopromide (IPD), Diclofenac (DCF), Cyclophosphamide (CFD) and Ifosfamide (IFD). Self-immobilization in a pellet shape was achieved for all fungal mycelia (which was the first time that this was reported for S. rugosoannulata, G. luteofolius, and A. erebia). Biodegradation achievement was greater than 90% for IPD with G. luteofolius and greater than 70% for CBZ with S. rugosoannulata, which suggests a great potential for this alternative biological treatment. Besides, this was the first report where fungal treatment achieved CFD and IFD removals greater than 20% for the treatment with T. versicolor, G. lucidum and S. rugosoannulata.

Pharmaceutical biodegradation under three anaerobic redox conditions evaluated by chemical and toxicological analyses

Biodegradation of pharmaceutically active compounds (PhACs) in the subsurface layer of constructed wetlands (CWs) under various anaerobic redox conditions is rarely studied. In this study, CW sediment microbial populations were enriched for PhAC biodegrading organisms. Biodegradation effectivity of a mixture of six PhACs (caffeine, CAF; naproxen, NAP; metoprolol, MET; propranolol, PRO; ibuprofen, IBP; carbamazepine, CBZ) and single compounds (CAF, NAP) was investigated under nitrate reducing, sulfate reducing, and methanogenic conditions using chemical and toxicological analyses. Biodegradation efficiencies varied strongly among the six PhACs and three redox conditions chosen. CAF and NAP were completely biodegraded under sulfate reducing and methanogenic conditions whereas biodegradation efficiencies of the other PhACs were much less (MET, PRO <20%; IBP, CBZ, negligible). CAF and NAP showed significantly lower biodegradation under nitrate reducing conditions than under the other two redox conditions. No difference was found in biodegradation efficiencies of CAF and NAP when present as single compound, or as a mixture with other PhACs. Different intermediates were observed, indicating different biodegradation pathways under different redox conditions and when the PhACs were present as single compound or in a mixture. From toxicological perspective, toxicity of PhACs and/or their intermediates to Vibrio fischeri was attenuated during the biodegradation process. Chemical and toxicological data showed positive correlations in principle component analysis, by which potentially toxic PhACs and intermediates are indicated for further ecotoxicological hazard assessment.

Study of anaerobic biodegradation of pharmaceuticals and personal care products: application of batch tests

This study evaluated three types of pharmaceuticals and personal care products (methylparaben, ibuprofen and triclosan) at concentration levels of 300, 500, 1000 and 2000 µg/L by implementing batch tests using anaerobic processes and granular biomass. The study aimed to identify the mechanisms of biodegradation and sorption in the degradation of these compounds. The inoculum was granular sludge from a laboratory-scale anaerobic reactor. The characterization results of the inoculum showed an anaerobic biomass with high activity, good sedimentation and a high percentage of organic matter. The results of the removal of the pollutants showed high degradation percentages for methylparaben (close to 99%), with negligible sorption in the sludge. The results also showed insignificant ibuprofen sorption but removal close to 0%. Triclosan showed high biomass sorption and low biodegradation. In addition, at the concentrations tested, none of the compounds had a negative or inhibitory effect on the microbial populations of the system.

Biodegradation of pharmaceuticals and endocrine disruptors with oxygen, nitrate, manganese (IV), iron (III) and sulfate as electron acceptors

Biodegradation of pharmaceuticals and endocrine disrupting compounds was examined in long term batch experiments for a period of two and a half years to obtain more insight into the effects of redox conditions. A mix including lipid lowering agents (e.g. clofibric acid, gemfibrozil), analgesics (e.g. diclofenac, naproxen), beta blockers (e.g. atenolol, propranolol), X-ray contrast media (e.g. diatrizoic acid, iomeprol) as well as the antiepileptic carbamazepine and endocrine disruptors (e.g. bisphenol A, 17α-ethinylestradiol) was analyzed in batch tests in the presence of oxygen, nitrate, manganese (IV), iron (III), and sulfate. Out of the 23 selected substances, 14 showed a degradation of >50% of their initial concentrations under aerobic conditions. The beta blockers propranolol and atenolol and the analgesics pentoxifylline and naproxen showed a removal of >50% under anaerobic conditions. In particular naproxen proved to be degradable with oxygen and under most anaerobic conditions, i.e. with manganese (IV), iron (III), or sulfate. The natural estrogens estriol, estrone and 17β-estradiol showed complete biodegradation under aerobic and nitrate-reducing conditions, with a temporary increase of estrone during transformation of estriol and 17β-estradiol. Transformation of 17β-estradiol under Fe(III)-reducing conditions resulted in an increase of estriol as well. Concentrations of clofibric acid, carbamazepine, iopamidol and diatrizoic acid, known for their recalcitrance in the environment, remained unchanged.

Laccases: Production, Expression Regulation, and Applications in Pharmaceutical Biodegradation.

Laccases are a family of copper-containing oxidases with important applications in bioremediation and other various industrial and biotechnological areas. There have been over two dozen reviews on laccases since 2010 covering various aspects of this group of versatile enzymes, from their occurrence, biochemical properties, and expression to immobilization and applications. This review is not intended to be all-encompassing; instead, we highlighted some of the latest developments in basic and applied laccase research with an emphasis on laccase-mediated bioremediation of pharmaceuticals, especially antibiotics. Pharmaceuticals are a broad class of emerging organic contaminants that are recalcitrant and prevalent. The recent surge in the relevant literature justifies a short review on the topic. Since low laccase yields in natural and genetically modified hosts constitute a bottleneck to industrial-scale applications, we also accentuated a genus of laccase-producing white-rot fungi, Cerrena, and included a discussion with regards to regulation of laccase expression.

Influence of humic acid addition on the degradation of pharmaceuticals by biofilms in effluent wastewater.

The degradation of organic micropollutants in wastewater treatment is suspected to depend on co-degradation i.e. be dependent on concentrations of substrate. This complicates predicting and modelling their fate. The effect of humic acid, as a model for complex organic substrate, was investigated in relation to the biodegradation of pharmaceuticals by suspended biofilm carriers adapted to polishing effluent water from a tertiary sewage treatment plant. Twelve out of 22 investigated pharmaceuticals were significantly biodegradable. The biodegradation rate constants of ten of those compounds were increasing with increased humic acid concentrations. At the highest humic acid concentration (30mgC/L), the biodegradation rate constants were four times higher than the biodegradation rate constants without added humic acid. This shows that the presence of complex substrate stimulates degradation via a co-metabolism-like mechanism and competitive inhibition does not occur. Increases of rate constant per mgC/L are tentatively calculated.

Biodegradation of carbamazepine and clarithromycin by Trichoderma harzianum and Pleurotus ostreatus investigated by liquid chromatography – high-resolution tandem mass spectrometry (FTICR MS-IRMPD)

In this study, the capability of pharmaceutical biodegradation of fungus Trichoderma harzianum was evaluated through the comparison with the well-known biodegradation capability of white-rot fungus Pleurotus ostreatus. The study was performed in aqueous phase under aerobic conditions, using two of the most frequently detected drugs in water bodies: carbamazepine and clarithromycin, with concentrations commonly found in treated wastewater (4μg/l and 0.03μg/l respectively). For the first time, we demonstrated that T. harzianum is able to remove carbamazepine and clarithromycin. The analyses were performed by reversed-phase liquid chromatography/mass spectrometry, using high-resolution Fourier-transform ion cyclotron resonance mass spectrometry upon electrospray ionization in positive ion mode. The high selectivity and mass accuracy provided by high-resolution mass spectrometry, allowed us to identify some unknown metabolites. On the basis of our study, the major metabolites detected in liquid culture treated by T. harzianum were: 14-hydroxy-descladinosyl- and descladinosyl-clarithromycin, which are pharmacologically inactive products not dangerous for the environment.

Biodegradation of pharmaceuticals in membrane aerated biofilm reactor for autotrophic nitrogen removal: A model-based evaluation

Wastewater treatment systems are a primary pathway for pharmaceuticals (PhACs) entering the aquatic environment, which require reliable prediction through integrating the specific biodegradation processes into modeling framework. As ammonia-oxidizing bacteria (AOB) are known to be able to catalyze the oxidation of a wide array of organic compounds, membrane aerated biofilm reactor (MABR) that remove nitrogen autotrophically through aerobic ammonia oxidation by AOB followed by Anammox may be capable of removing PhACs. In this work, a mathematical model was constructed to assess the PhAC biodegradation and removal potential in MABR under various operational conditions. The cometabolic biodegradation kinetics was used to model PhAC biodegradation by both AOB and heterotrophs. Simulations show that AOB play a major role in PhAC biodegradation with minor contribution from heterotrophs under the influent condition with high-strength ammonium. Both oxygen surface loading and influent surface loading (or hydraulic retention time (HRT)) are found to significantly impact the simultaneous removal of PhACs and total nitrogen (TN) at the optimal biofilm thickness of 750μm. Approximately 80% of PhACs can be removed in the MABR under operational conditions (oxygen surface loading and HRT) optimal for TN removal with above 75% TN removal achieved. When treating low-strength nitrogenous wastewater, PhAC removal efficiency decreases substantially due to the lower abundance of AOB. The presence of organic matters would substantially increase PhAC removal efficiency mainly via heterotrophs biodegradation pathway, but would suppress the Anammox activity.

Biodegradation of pharmaceuticals in hospital wastewater by staged Moving Bed Biofilm Reactors (MBBR)

Hospital wastewater represents a significant input of pharmaceuticals into municipal wastewater. As Moving Bed Biofilm Reactors (MBBRs) appear to remove organic micro-pollutants, hospital wastewater was treated with a pilot plant consisting of three MBBRs in series. The removal of pharmaceuticals was studied in two experiments: 1) A batch experiment where pharmaceuticals were spiked to each reactor and 2) a continuous flow experiment at native concentrations. DOC removal, nitrification as well as removal of pharmaceuticals (including X-ray contrast media, β-blockers, analgesics and antibiotics) occurred mainly in the first reactor. In the batch experiment most of the compounds followed a single first-order kinetics degradation function, giving degradation rate constants ranged from 5.77 × 10−3 to 4.07 h−1, from −5.53 × 10−3 to 9.24 × 10−1 h−1 and from 1.83 × 10−3 to 2.42 × 10−1 h−1 for first, second and third reactor respectively. Generally, the highest removal rate constants were found in the first reactor while the lowest were found in the third one. This order was inverted for most compounds, when the removal rate constants were normalized to biomass, indicating that the last tank had the most effective biofilms. In the batch experiment, 21 out of 26 compounds were assessed to be degraded with more than 20% within the MBBR train. In the continuous flow experiment the measured removal rates were lower than those estimated from the batch experiments.

Biodegradation of pharmaceuticals in hospital wastewater by a hybrid biofilm and activated sludge system (Hybas)

Hospital wastewater contributes a significant input of pharmaceuticals into municipal wastewater. The combination of suspended activated sludge and biofilm processes, as stand-alone or as hybrid process (hybrid biofilm and activated sludge system (Hybas™)) has been suggested as a possible solution for hospital wastewater treatment. To investigate the potential of such a hybrid system for the removal of pharmaceuticals in hospital wastewater a pilot plant consisting of a series of one activated sludge reactor, two Hybas™ reactors and one moving bed biofilm reactor (MBBR) has been established and adapted during 10months of continuous operation. After this adaption phase batch and continuous experiments were performed for the determination of degradation of pharmaceuticals. Removal of organic matter and nitrification mainly occurred in the first reactor. Most pharmaceuticals were removed significantly. The removal of pharmaceuticals (including X-ray contrast media, β-blockers, analgesics and antibiotics) was fitted to a single first-order kinetics degradation function, giving degradation rate constants from 0 to 1.49h−1, from 0 to 7.78×10−1h−1, from 0 to 7.86×10−1h−1 and from 0 to 1.07×10−1h−1 for first, second, third and fourth reactors respectively. Generally, the highest removal rate constants were found in the first and third reactors while the lowest were found in the second one. When the removal rate constants were normalized to biomass amount, the last reactor (biofilm only) appeared to have the most effective biomass in respect to removing pharmaceuticals. In the batch experiment, out of 26 compounds, 16 were assessed to degrade more than 20% of the respective pharmaceutical within the Hybas™ train. In the continuous flow experiments, the measured removals were similar to those estimated from the batch experiments, but the concentrations of a few pharmaceuticals appeared to increase during the first treatment step. Such increase could be attributed to de-conjugation or formation from other metabolites.

Uncertainty and sensitivity analyses using GLUE when modeling inhibition and pharmaceutical cometabolism during nitrification

The influence of uncertainties in biokinetic parameters for ammonia and nitrite oxidizing bacteria on the performance of a two-step nitrification model was evaluated using the Generalized Uncertainty Estimation (GLUE) technique. The predictive capability of behavioral simulations generated using GLUE was assessed utilizing data from experiments comparing nitrification in the presence and absence of two pharmaceuticals – atenolol or sotalol. Results suggest that GLUE cannot account for model structural error arising when ammonia oxidation is competitively inhibited. Use of a competitive inhibition model for ammonia oxidation (i.e., correction of the model structural error), however, enables GLUE to generate meaningful uncertainty intervals. While GLUE is used in the present study, other uncertainty analysis techniques are likely to be similarly unable to account for model structural errors. Thus, results from this study emphasize the importance of model selection for efficacious uncertainty analysis. The behavioral simulations generated using GLUE based on application of the correct model was subsequently used to evaluate the sensitivity of transformation coefficients employed to describe the cometabolism of atenolol by ammonia oxidizing bacteria (AOB). Sensitivity was assessed by computing nonparametric elasticities of the cometabolism transformation coefficients to biokinetic parameters selected to describe nitrification in a novel application of a generalized nonparametric analysis. Results suggest that the AOB-growth related transformation coefficient of atenolol is relatively insensitive to variation in ammonia and nitrite oxidizing biokinetic parameters. In contrast, the non-growth related transformation coefficient describing atenolol cometabolism appears to be sensitive to the specific growth rate of AOB. Elasticities are used to assess whether estimates of atenolol-AOB cometabolic biodegradation coefficients from lab-scale experiments could be used more generally. This novel application of elasticities to biological wastewater process modeling suggests that seasonal temperature variations may be an important factor in pharmaceutical biodegradation during biological wastewater treatment.

Biodegradation and Cometabolic Modeling of Selected Beta Blockers during Ammonia Oxidation

Accurate prediction of pharmaceutical concentrations in wastewater effluents requires that the specific biochemical processes responsible for pharmaceutical biodegradation be elucidated and integrated within any modeling framework. The fate of three selected beta blockers-atenolol, metoprolol, and sotalol-was examined during nitrification using batch experiments to develop and evaluate a new cometabolic process-based (CPB) model. CPB model parameters describe biotransformation during and after ammonia oxidation for specific biomass populations and are designed to be integrated within the Activated Sludge Models framework. Metoprolol and sotalol were not biodegraded by the nitrification enrichment culture employed herein. Biodegradation of atenolol was observed and linked to the activity of ammonia-oxidizing bacteria (AOB) and heterotrophs but not nitrite-oxidizing bacteria. Results suggest that the role of AOB in atenolol degradation may be disproportionately more significant than is otherwise suggested by their lower relative abundance in typical biological treatment processes. Atenolol was observed to competitively inhibit AOB growth in our experiments, though model simulations suggest inhibition is most relevant at atenolol concentrations greater than approximately 200 ng·L(-1). CPB model parameters were found to be relatively insensitive to biokinetic parameter selection suggesting the model approach may hold utility for describing pharmaceutical biodegradation during biological wastewater treatment.

Modelling the biodegradation of non-steroidal anti-inflammatory drugs (NSAIDs) by activated sludge and a pure culture

A model describing ibuprofen and ketoprofen biodegradation by activated sludge from three different wastewater treatment plants (WWTP) was developed in this study. This model successfully described the biodegradation profiles observed at two different initial concentrations of each compound, where a lag-phase was observed prior to the biodegradation of each compound. Twelve ibuprofen and ketoprofen degrading isolates were identified in this study from the WWTP sludge showing the best removal performance. One of these isolates was characterised via another model, where biodegradation was dependent on biomass growth rate as well as the ibuprofen concentration. The fact that different models were needed to describe the biodegradation by activated sludge and a pure culture suggests that the biodegradation of non-steroidal anti-inflammatory drugs (NSAIDs) depends on the microbial community, thus pharmaceutical biodegradation models may require adaptation depending upon the system. This study provides an advance towards modelling pharmaceutical biodegradation in WWTPs.

Enantioselective biodegradation of pharmaceuticals, alprenolol and propranolol, by an activated sludge inoculum

Biodegradation of chiral pharmaceuticals in the environment can be enantioselective. Thus quantification of enantiomeric fractions during the biodegradation process is crucial for assessing the fate of chiral pollutants. This work presents the biodegradation of alprenolol and propranolol using an activated sludge inoculum, monitored by a validated enantioselective HPLC method with fluorescence detection. The enantioseparation was optimized using a vancomycin-based chiral stationary phase under polar ionic mode. The method was validated using a minimal salts medium inoculated with activated sludge as matrix. The method was selective and linear in the range of 10–800ng/ml, with a R2>0.99. The accuracy ranged from 85.0 percent to 103 percent, the recovery ranged from 79.9 percent to 103 percent, and the precision measured by the relative standard deviation (RSD) was <7.18 percent for intra-batch and <5.39 percent for inter-batch assays. The limits of quantification and detection for all enantiomers were 10ng/ml and 2.5ng/ml, respectively. The method was successfully applied to follow the biodegradation of the target pharmaceuticals using an activated sludge inoculum during a fifteen days assay. The results indicated slightly higher biodegradation rates for the S-enantiomeric forms of both beta-blockers. The presence of another carbon source maintained the enantioselective degradation pattern while enhancing biodegradation extent up to fourteen percent.

Incorporation of in silico biodegradability screening in early drug development—a feasible approach?

The concentration of a pharmaceutical found in the environment is determined by the amount used by the patient, the excretion and metabolism pattern, and eventually by its persistence. Biological degradation or persistence of a pharmaceutical is experimentally tested rather late in the development of a pharmaceutical, often shortly before submission of the dossier to regulatory authorities. To investigate whether the aspect of persistence of a compound could be assessed early during drug development, we investigated whether biodegradation of pharmaceuticals could be predicted with the help of in silico tools. To assess the value of in silico prediction, we collected results for the OECD 301 degradation test ("ready biodegradability") of 42 drugs or drug synthesis intermediates and compared them to the prediction of the in silico tool BIOWIN. Of these compounds, 38 were predictable with BIOWIN, which is a module of the Estimation Programs Interface (EPI) Suite™ provided by the US EPA. The program failed to predict the two drugs which proved to be readily biodegradable in the degradation tests. On the other hand, BIOWIN predicted two compounds to be readily biodegradable which, however, proved to be persistent in the test setting. The comparison of experimental data with the predicted one resulted in a specificity of 94% and a sensitivity of 0%. The results of this study do not indicate that application of the biodegradation prediction tool BIOWIN is a feasible approach to assess the ready biodegradability during early drug development.

Biodegradation of pharmaceuticals by Rhodococcus rhodochrous and Aspergillus niger by co-metabolism

This work investigated the possible fate of pharmaceuticals in the environment that are known to be resistant to biodegradation. A co-metabolism approach, adding a readily degradable carbon source, was used to study the biodegradation of some pharmaceuticals. The pharmaceuticals selected were all known to be micro pollutants and frequently used by humans. The microorganisms used primarily were Rhodococcus rhodochrous, known to co-metabolize difficult to degrade hydrocarbons and Aspergillus niger. Because of the long periods of time required for the degradation experiments after growth had reached the stationary phase, it was found to be necessary to correct for water loss from the media. Co-metabolism of carbamazepine, sulfamethizole and sulfamethoxazole was observed and as much as 20% of these compounds could be removed. Small amounts of stable metabolites were observed during the degradation of some of these drugs and these were different from the metabolites obtained from abiotic degradation. A metabolite arising from the biodegradation of sulfamethoxazole by R. rhodochrous was identified.