The Food and Drug Administration (FDA) Center for Drug Evaluation and Research, Office of Pharmaceutical Science, Informatics and Computational Safety Analysis Staff's Maximum Recommended Daily Dose (FDAMDD) database contains values for over 1200 pharmaceuticals listed in Martindale: The Extra Pharmacopoeia (1973, 1983, and 1993) and The Physicians' Desk Reference (1995 and 1999). Some classes of chemicals were excluded from the FDAMDD database due to their unsuitability for most QSAR modeling programs. These were inorganic chemicals, high molecular weight polymers (>5000 Daltons), fibers, salts, mixtures of organic chemicals, and small molecules (<100 Daltons). FDAMDD is the non-proprietary portion of the database that was used in the QSAR analysis reported in the Main Citation. DSSTox FDAMDD has fewer substance records than the original MRDD Source database due to consolidation of partial structures (i.e., complexed entities) into a single record and elimination of duplicate entries. DSSTox FDAMDD also differs from the MRDD Source database in presenting complete structural information pertaining to the actual salt or complexed form corresponding to the listed ChemicalName and CASRN. According to the Source authors, there are a number of cases where multiple related forms or derivatives of a drug were listed as separate records but were assumed to fall under the same clinical toxicity assessment and, therefore, assigned the same Dose_MRDD_mg activity value. For the DSSTox FDAMDD, we have labeled these derivatives in the ChemClass_MRDD_grouping field and provide their counts in the ChemicalReplicateCount field to highlight their special nature.

Maximum recommended daily dose (or maximum recommended therapeutic dose) values were determined from pharmaceutical clinical trials that employed an oral route of exposure and daily treatments, usually for 3-12 months. Drugs were given as single or divided dose treatment regimens to achieve desired pharmacological effects. Roughly 5% of the pharmaceuticals in the FDAMDD data file were antineoplastics and anesthetics and were administered intravenously and/or intramuscularly. When separate MRDDs were reported for different routes of exposure, only the oral MRDD was included in the data file and only MRDD values reported for the average adult patient were used. Pharmaceuticals that are administered orally are usually tested over a limited range of doses and have MRDDs reported as mg/day. The mg/day unit was converted to mg/kg-body weight (bw)/day based upon an average adult weighing 60 kg. In contrast, the dose unit for most antineoplastic drug MRDDs is reported as mg/m2 which was converted to mg/kg-bw/day using the formula mg/kg-bw/day = mg/m2/37 for an average adult. Additionally, a few drugs had MRDDs reported in parts per million (ppm) which were converted to mg/kg-bw/day on the basis that 1000 ppm equals 25 mg/kg-bw/day for an average 60 kg adult. Activity Score is mapping of LOG10(1/Dose_MRDD_mmol) spanning activity range [MIN, MAX] onto Integer 1-100 Activity range, where 100 is highest potency and 1 is lowest potency: ActivityScore = 100 * INTEGER[(LOGINV_MRDD_mmol - MIN)/(MAX # MIN)]. Activity Outcome is "active" for all substances, since Dose_MRDD_mmol is reported for all substances.

DSSTox (FDAMDD): FDA Maximum (Recommended) Daily Dose Database

To access complete SD file and documentation, refer to the DSSTox FDAMDD Download Page

For more information and description pertaining to this assay, see the FDA CDER Website

Main Citation: Matthews, E.J., N.L. Kruhlak, R.D. Benz, and J.F. Contrera (2004) Assessment of the health effects of chemicals in humans: I. QSAR estimation of the maximum recommended therapeutic dose (MRTD) and no effect level (NOEL) of organic chemicals based on clinical trial data, Current Drug Discovery Technologies, 1(1): 61-76.