J: Antiinfectives for systemic use
Drugs given systemically against an invading organism, bacteria, fungi, mycobacteria and viruses, plus immune sera and vaccines under the same letter [1]. The potency term is a property of the pathogen isolate, its MIC, rather than of the patient (see PKPD) [2].
Fleming’s mould plate of 1928 became a medicine only in February 1941, when Florey’s Oxford group treated a constable, Albert Alexander [3,4]. He responded, but penicillin re-purified from his urine was not enough to keep the course going, the supply ran out and he died [3,5]. Fleming, Florey and Chain shared the 1945 Nobel Prize [5].
| Level 2 code | Description | In plain terms | Example drug |
|---|---|---|---|
| J01 | Antibacterials for systemic use | Amoxicillin (J01CA04) / ceftriaxone (J01DD04) | |
| J02 | Antimycotics for systemic use | antifungals taken into the bloodstream | Fluconazole (J02AC01) / caspofungin (J02AX04) |
| J04 | Antimycobacterials | drugs against tuberculosis and leprosy | Rifampicin (J04AB02) / isoniazid (J04AC01) |
| J05 | Antivirals for systemic use | Dolutegravir (J05AJ03) / sofosbuvir (J05AP08) | |
| J06 | Immune sera and immunoglobulins | ready-made antibodies given as instant protection | Normal human immunoglobulin for intravascular administration (J06BA02) / nirsevimab (J06BD08) |
| J07 | Vaccines | Influenza, inactivated, split virus or surface antigen (J07BB02) / covid-19, RNA-based vaccine (J07BN01) |
Modeling notes
Endpoint. For antibacterials it is bacterial count, log CFU, from time-kill or animal infection experiments [6,7]. For J05 it is plasma viral load [8,9].
Easy to overlook. MIC is a discrete two-fold scale carrying real measurement error [10]. Unbound concentration is the active one, yet there is no standard way to account for protein binding in in vitro pharmacodynamic testing [11]. After hepatitis A vaccination, antibody titres decay multiphasically, set by the lifespans of antibody and of short- and long-lived plasma cells [12].
Mechanistic extrapolation. PBPK has been applied to antiretrovirals where trials are hard: exposure in pregnancy [13] and release from long-acting intramuscular depots [14]. For J04 the hollow fiber system is qualified by the EMA as a methodology supporting the development of antituberculosis regimens [15].