Target-mediated drug disposition model for drugs with two binding sites that bind to a target with one binding site

AbstractThe paper extended the TMDD model to drugs with two identical binding sites (2-1 TMDD). The quasi-steady-state (2-1 QSS), quasi-equilibrium (2-1 QE), irreversible binding (2-1 IB), and Michaelis –Menten (2-1 MM) approximations of the model were derived. Using simulations, the 2-1 QSS approximation was compared with the full 2-1 TMDD model. As expected and similarly to the standard TMDD for monoclonal antibodies (mAb), 2-1 QSS predictions were nearly identical to 2-1 TMDD predictions, exce pt for times of fast changes following initiation of dosing, when equilibrium has not yet been reached. To illustrate properties of new equations and approximations, several variations of population PK data for mAbs with soluble (slow elimination of the complex) or membrane-bound (fast elimination o f the complex) targets were simulated from a full 2-1 TMDD model and fitted to 2-1 TMDD models, to its approximations, and to the standard (1-1) QSS model. For a mAb with a soluble target, it was demonstrated that the 2-1 QSS model provided nearly identical description of the observed (simulated) fr ee drug and total target concentrations, although there was some minor bias in predictions of unobserved free target concentrations. The standard QSS approximation also provided a good description of the observed data, but was not able to distinguish between free drug concentrations (with no target attached and both binding site free) and partially bound drug concentrations (with one of ...
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research

Related Links:

Source: Acta Neurochirurgica - Category: Neurosurgery Source Type: research
Source: Acta Neurochirurgica - Category: Neurosurgery Source Type: research
Source: Acta Neurochirurgica - Category: Neurosurgery Source Type: research
Source: Acta Neurochirurgica - Category: Neurosurgery Source Type: research
We present the case of a girl who underwent VPH for hemimegalencephaly in early infancy. Postoperatively, she developed unexpected seizures of mesio-temporal origin. Stereo-EEG provided arguments for an amygdalar origin. High-resolution MRI with tractography confirmed the presence of the amygdalo-fugal pathway to be responsible of epileptic discharges propagation. She became seizure-free after temporal resection.
Source: Acta Neurochirurgica - Category: Neurosurgery Source Type: research
Source: Acta Neurochirurgica - Category: Neurosurgery Source Type: research
ConclusionWe successfully utilized biportal endoscopy to decompress the combined lumbar lateral recess, foraminal, and extraforaminal lesions using a contralateral sublaminar approach.
Source: Acta Neurochirurgica - Category: Neurosurgery Source Type: research
We describe a patient with a long history of seizures and a remote status epilepticus event. On magnetic resonance imaging, a presumed left temporal lobe tumor was observed. On neurosurgical consultation, the lesion was identified as a chronic mesial temporal lobe herniation. The patient lacked history that would suggest risk of cerebral herniation. Accurately identifying the patient ’s chronic temporal lobe herniation radiographically likely saved this patient from unnecessary surgery or biopsy and allowed the patient to receive appropriate conservative care.
Source: Acta Neurochirurgica - Category: Neurosurgery Source Type: research
Source: Acta Neurochirurgica - Category: Neurosurgery Source Type: research
ConclusionsThe study represents the much-needed, large-volume, epidemiological profile of HI from an LMIC, highlighting the suboptimal utilization of peripheral healthcare systems. Strengthening and integrating these facilities with the tertiary centers in a hub and enhanced spoke model, task sharing design, and efficient back-referrals promise effective neurotrauma care while avoiding overburden in the tertiary centers. Better implementation of road safety laws also has the potential to reduce the burden of HI.
Source: Acta Neurochirurgica - Category: Neurosurgery Source Type: research
More News: Drugs & Pharmacology | Men