Abstract：
:One of the challenges with predictive modeling is how to quantify the reliability of the models' predictions on new objects. In this work we give an introduction to conformal prediction, a framework that sits on top of traditional machine learning algorithms and which outputs valid confidence estimates to predictions from QSAR models in the form of prediction intervals that are specific to each predicted object. For regression, a prediction interval consists of an upper and a lower bound. For classification, a prediction interval is a set that contains none, one, or many of the potential classes. The size of the prediction interval is affected by a user-specified confidence/significance level, and by the nonconformity of the predicted object; i.e., the strangeness as defined by a nonconformity function. Conformal prediction provides a rigorous and mathematically proven framework for in silico modeling with guarantees on error rates as well as a consistent handling of the models' applicability domain intrinsically linked to the underlying machine learning model. Apart from introducing the concepts and types of conformal prediction, we also provide an example application for modeling ABC transporters using conformal prediction, as well as a discussion on general implications for drug discovery.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Alvarsson J,Arvidsson McShane S,Norinder U,Spjuth Odoi
10.1016/j.xphs.2020.09.055subject
Has Abstractpub_date
2021-01-01 00:00:00pages
42-49issue
1eissn
0022-3549issn
1520-6017pii
S0022-3549(20)30589-Xjournal_volume
110pub_type
杂志文章abstract：:The period of time after administration over which blood level measurements are required to obtain a reliable bioavailability comparison of two or more formulations of the same drug was considered by the analysis of bioavailability data taken from the literature. The drugs examined, selected to represent a range of ab...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600640921
更新日期：1975-09-01 00:00:00
abstract：:The objective of this study was to determine the relative importance of metabolism by cytochrome P450 (CYP) enzymes versus efflux by P-glycoprotein (P-gp) in restricting the intestinal mucosal permeation of cyclic prodrugs (AOA-DADLE, CA-DADLE, OMCA-DADLE) of the opioid peptide DADLE (H-Tyr-D-Ala-Gly-Phe-D-Leu-OH). AO...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21424
更新日期：2009-01-01 00:00:00
abstract：:The application of drug ion-selective electrodes as sensors for the direct determination of the released drug in a continuous-flow analyzer for automated dissolution studies is described. Flow-through electrodes, selective to chlorpromazine, amitriptyline, propantheline, cimetidine, and ranitidine, have been construct...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600760911
更新日期：1987-09-01 00:00:00
abstract：:The affinity chromatographic technique was used to study the interaction of bovine serum albumin and salicylic acid at 3.3 +/- 1.1 degrees. Beaded agarose gel, on which the albumin was immobilized by covalent linkage, was packed in a column as an affinity adsorbent. Frontal analysis was performed on this column to eva...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670737
更新日期：1978-07-01 00:00:00
abstract：:Nitroglycerin is rapidly lost from solution when incubated with red blood cells or whole blood. The assumption that the loss is enzymatic in nature may not be true, since no major metabolite is detected during this incubation. Explanation on the basis of a chemical reaction is also difficult, since the products of the...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600720403
更新日期：1983-04-01 00:00:00
abstract：:The intrinsic factor-mediated binding of cyanocobalamin to cholestyramine was studied in vitro under varying conditions of pH, added electrolyte, and bile salt. The intrinsic factor-cyanocobalamin complex was adsorbed strongly by the resin at pH 3 in the presence of neutral salt and low concentrations of glycocholic a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600671132
更新日期：1978-11-01 00:00:00
abstract：:The aim of this study is to explore hot melt extrusion (HME) as a solvent-free drug loading technique for preparation of stable amorphous solid dispersions using mesoporous silica (PSi). Ibuprofen and carvedilol were used as poorly soluble active pharmaceutical ingredients (APIs). Due to the high friction of an API:PS...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.05.039
更新日期：2018-01-01 00:00:00
abstract：:A series of even numbered fatty acid esters (C2-C18) of p-[N,N-bis(2-chloroethyl)amino]phenol were synthesized and evaluated as to acute toxicity as well as effectiveness against L-1210 mouse leukemia. The acetate through the decanoate derivatives demonstrated toxicity between 2 and 3 times that of phenol mustard in H...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600710713
更新日期：1982-07-01 00:00:00
abstract：:The organic extract of the whole plant Xanthorhiza simplicissima was found to exhibit good activity against the AIDS-related opportunistic pathogens Candida albicans, Cryptococcus neoformans, and Mycobacterium intracellularae. Bioassay-directed fractionation of the extract led to the isolation of the known alkaloid be...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600830327
更新日期：1994-03-01 00:00:00
abstract：:Virtually all biological variables, including those affected by drugs, are subject to adaptive self regulation. In the description of the pharmacodynamics (PD) of drugs, it may be necessary to consider the endogenous control system (ECS) as an integral part of the PD. A PDECS model based on system analysis principles ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600820310
更新日期：1993-03-01 00:00:00
abstract：:Inhibition of endogenous prostacyclin and thromboxane biosynthesis by aspirin is critically dose-dependent in humans. Gastrointestinal and hepatic hydrolysis may limit systemic availability of aspirin, especially in low doses, perhaps contributing to the biochemical selectivity of aspirin. Existing analytical methods ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600740217
更新日期：1985-02-01 00:00:00
abstract：:Elucidation of the most stable form of an active pharmaceutical ingredient (API) is a critical step in the development process. Polymorph screening for an API with a complex polymorphic profile can present a significant challenge. The presented case illustrates an extensively polymorphic compound with an additional pr...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22230
更新日期：2010-09-01 00:00:00
abstract：:Lysosomes are acidic intracellular organelles that can extensively sequester basic lipophilic drugs due to pH and membrane partitioning, and therefore may significantly influence subcellular drug concentrations. Current in vitro methods for lysosomal drug sequestration evaluation typically lack the ability to accurate...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.05.026
更新日期：2020-09-01 00:00:00
abstract：:To date, research on the effect of single nucleotide polymorphisms (SNPs) on P-glycoprotein (P-gp) expression and functionality has rendered inconsistent results. This study systematically evaluates the impact of MDR1 haplotypes (1236/2677, 1236/3435, 2677/3435, 1236/2677/3435) on P-gp functionality compared to indivi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20717
更新日期：2006-10-01 00:00:00
abstract：:Maintaining good content uniformity (CU) is a significant challenge for low-dose oral tablets in particular when using direct compression (DC). Using 6 model active pharmaceutical ingredients, we show that a platform DC tablet formulation suitable for developing low-dose API with excellent CU can be developed. This pl...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.03.005
更新日期：2017-07-01 00:00:00
abstract：:Mixing Fungizone with a fat emulsion used for nutritional purpose (Intralipid or Lipofundin ) was reported to decrease Amphotericin B (AmB) toxicity in clinical use. In an effort to understand the reason for this phenomenon, spectral and morphological analyses were done for the Fungizone and Fungizone /Lipofundin admi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10223
更新日期：2002-11-01 00:00:00
abstract：:A general spectroscopic method is described that might be applied to validating amino acid sequences in peptides and protein fragments with a view to it becoming a routine procedure with which to characterize biotechnology drug products. The tripeptides are the L-enantiomers of GGA, GGH, GGI, GGL, GGF, GHG, LGG, and Y...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js980393o
更新日期：1999-07-01 00:00:00
abstract：:(14)N nuclear quadrupole resonance (NQR) in two known polymorphs of famotidine was measured. At room temperature, seven quadrupolar sets of transition frequencies (ν(+), ν(-), and ν(0)) corresponding to seven different nitrogen sites in the crystal structure of each of the two polymorphs were found. This confirms the ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23956
更新日期：2014-09-01 00:00:00
abstract：:We previously reported nonaqueous silicone elastomer gels (SEGs) for sustained vaginal administration of the CCR5-targeted entry inhibitor maraviroc (MVC). Here, we describe chemically modified SEGs (h-SEGs) in which the hydrophobic cyclomethicone component was partially replaced with relatively hydrophilic silanol-te...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23913
更新日期：2014-05-01 00:00:00
abstract：:The kinetics of acetylation of alcohols by acetyl chloride and acetic anhydride, with N-methylimidazole as the catalyst, were studied in acetonitrile solution at 25 degrees; some measurements were also made with 4-dimethylaminopyridine as the catalyst. The acetic anhydride-N-methylimidazole system proceeds entirely by...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600710503
更新日期：1982-05-01 00:00:00
abstract：:A procedure was developed for the separation and selective quantitative determination of the (S)(+)- and (R)(-)-enantiomers of the racemic anti-inflammatory drug carprofen as their diastereomeric l-(-)-alpha-methylbenzylamides. These derivatives are obtained in equivalent yields by reacint purified 14C-carprofen from ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600681021
更新日期：1979-10-01 00:00:00
abstract：:Thirty-four vasodilators were screened in several in vitro biochemical assays related to smooth muscle excitation-contraction coupling, binding to beta 1-,beta 2-, and alpha-adrenergic receptors, inhibition of phosphodiesterase activity, and antagonism of calcium accumulation. Isoproterenol and perhexiline only exhibi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600710123
更新日期：1982-01-01 00:00:00
abstract：:The described simple, accurate, and precise reversed-phase high-pressure liquid chromatographic procedure is in excellent agreement with 1-octanol shake-flask partition or distribution coefficients over a 3.5 log range. A chemically bonded octadecylsilane support is persilated and coated with 1-octanol. With 1-octanol...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600671008
更新日期：1978-10-01 00:00:00
abstract：:Amphiphilic cyclodextrins (CDs) are biocompatible derivatives of natural CDs and are able to form nanoparticles or polyplexes spontaneously. In this study, nanoparticles prepared from nonionic (6OCaproβCD) or cationic amphiphilic CD (PC βCDC6) were used comparatively to develop nanoparticles intended for breast cancer...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.06.021
更新日期：2016-10-01 00:00:00
abstract：:Cephalosporins are among the most frequently used broad-spectrum antimicrobial agents. Ceftazidime is a semisynthetic β-lactam antibiotic for parenteral administration widely used in the clinical practice, which has been categorized as a third-generation cephalosporin antibiotic. This drug crystallizes as a pentahydra...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.11.018
更新日期：2020-03-01 00:00:00
abstract：:The objective of this study was to establish the optimal blood concentrations of the potent P-glycoprotein (P-gp) inhibitor GF120918 (Elacridar) required to achieve maximal knockout of this efflux transporter in the blood-brain barrier (BBB) of mice, rats, and guinea pigs. Genetic mdr1a/b(-/-) knockout mice and "chemi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20658
更新日期：2006-09-01 00:00:00
abstract：:Avoiding unwanted immunogenicity is of key importance in the development of therapeutic drug proteins. Animal models are of less predictive value because most of the drug proteins are recognized as foreign proteins. However, different methods have been developed to obtain immunotolerant animal models. So far, the immu...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23447
更新日期：2013-03-01 00:00:00
abstract：:For development and optimization of protein formulation sensitive analytical tools are required to follow both aggregation and changes in protein structure. The latter can be seen as the beginning of physical instability leading to aggregation. The focus of this work laid on the development of a novel analysis simulta...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22808
更新日期：2012-02-01 00:00:00
abstract：:Biphenylalkyl monoesters of succinic and related acids represent a potent new class of cyclic AMP phosphodiesterase inhibitors. The biphenyl group is necessary for potent inhibition. The spatial relationship of the carboxyl and ester groups and alkyl chain length are important to inhibitory potency. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600680732
更新日期：1979-07-01 00:00:00
abstract：:In vitro iontophoretic administration of drugs through a microporous polyolefin membrane with hydrophilic urethane polymerfilled pores was done for the ionized drugs dexamethasone sodium phosphate, hydrocortisone sodium phosphate, and prednisolone sodium succinate, and for a nonionizable drug cortisone acetate. Curren...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600780308
更新日期：1989-03-01 00:00:00
