“Phase I and Phase II” Drug Metabolism: Terminology that we Should Phase Out?
Bibliographic record
Abstract
Richard Tecwyn Williams (1909–1979) was one of the founders of the study of drug metabolism. His monograph “Detoxication Mechanisms: The Metabolism of Drugs and Allied Organic Compounds” (Williams, 1949) helped to establish the study of drug and toxicant metabolism as a scientific discipline. Williams summarized the then-known processes of metabolism of xenobiotics, organizing the subject according to classes of foreign chemicals, rather than according to classes of biotransformations. The second edition of the book (Williams, 1959), was again organized by chemical class. However, in a concluding chapter, Williams introduced the idea of distinguishing between two categories of biotransformation, which he called “Phase I” and “Phase II” reactions. The following excerpt from the book defines this distinction. “In the first chapter it was stated that the reactions of foreign compounds in vivo could be divided into four classes, oxidations, reductions, hydrolyses and syntheses. All the reactions of foreign compounds can, in fact, be discussed broadly in terms of these four classes of reactions. The oxidations include not only the commonly accepted oxidations such as the conversion of C-methyl groups, alcohols and aldehydes to carboxylic acids, but also oxidative O- and N-dealkylations, oxidative deaminations, aromatic hydroxylations, dehydrochlorinations, etc… . It appears that the metabolism of most foreign compounds occurs in two phases. The first phase involves oxidations, reductions or hydrolyses or a combination of any of these three, and for convenience these may be termed “phase I reactions”; the second phase (“phase II reactions”) consists of synthesis, mainly conjugations such as glucuronide, ethereal sulphate, thiocyanate, and hippuric acid formation. In the first phase, biologically active compounds may be inactivated or have
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".