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How a drug moves through the body: how much is absorbed, how high the blood level gets, how long it lasts (half-life) and how it is cleared. These numbers decide the dose, the schedule and whether a pill can be taken with food or other medicines.
Antibodies have half-lives of 2-4 weeks and are dosed every 2-6 weeks, often now at flat doses (pembrolizumab 400 mg q6w) rather than by weight; small molecules are dosed daily and interact with CYP3A4 inhibitors, acid suppressants and food; chemotherapy is dosed by body surface area with organ-function adjustments. Exposure-response analyses link drug levels to efficacy and toxicity and underpin Project Optimus's push to find optimal rather than maximal doses; therapeutic drug monitoring is used for busulfan, methotrexate and increasingly for TKIs. Radiopharmaceutical PK determines tumour versus kidney and marrow dose (dosimetry). Poor oral bioavailability has ended more than one promising drug's development.
Explains why a patient on cancer drugs that inhibit P-glycoprotein or CYP3A4 is at higher risk from ivermectin than a healthy volunteer, and why veterinary doses are dangerous.
A reminder that ivermectin interacts with cancer drugs: the dose that a healthy adult tolerates can poison a patient whose liver enzymes are already occupied by a kinase inhibitor.
Veber's rules, alongside Lipinski's rule of five, are used across the industry to decide whether a molecule can become a pill. They set the boundaries within which most oral kinase inhibitors and other targeted cancer drugs were designed, and the current push into larger molecules such as PROTACs and macrocycles is partly an effort to work beyond them.
Shares Maximum tolerated dose (MTD), Recommended phase 2 dose (RP2D), Therapeutic index (therapeutic window), Project Optimus.
Shares Maximum tolerated dose (MTD), Recommended phase 2 dose (RP2D), Project Optimus.
Shares TPMT and NUDT15 genotyping before thiopurines, UGT1A1 genotyping before irinotecan, DPYD genotyping and DPD phenotyping before fluoropyrimidines.
Shares ICONIC: ivermectin combined with immune checkpoint inhibition in cancer (University of Florida phase 2), Ivermectin.
Shares Therapeutic index (therapeutic window), Dose reduction, interruption and discontinuation.
Shares Therapeutic index (therapeutic window), Dose reduction, interruption and discontinuation.
Shares ICONIC: ivermectin combined with immune checkpoint inhibition in cancer (University of Florida phase 2), Ivermectin.
Shares Exposure-response modelling with a pre-set target exposure before any dose is chosen, Project Optimus.