ABSTRACT
The creation of a pharmacokinetic (PK) curve, which follows the plasma concentration of an administered drug as a function of time, is a critical aspect of the drug development process and includes such information as the drug's bioavailability, clearance, and elimination half-life. Prior to a drug of interest gaining clearance for use in human clinical trials, research is performed during the preclinical stages to establish drug safety and dosing metrics from data obtained from the PK studies. Both in vivo animal models and in vitro platforms have limitations in predicting human reaction to a drug due to differences in species and associated simplifications, respectively. As a result, in silico experiments using computer simulation have been implemented to accurately predict PK parameters in human studies. This review assesses these three approaches (in vitro, in vivo, and in silico) when establishing PK parameters and evaluates the potential for in silico studies to be the future gold standard of PK preclinical studies.
Subject(s)
Models, Biological , Pharmaceutical Preparations/analysis , Pharmaceutical Preparations/metabolism , Pharmacokinetics , Animals , Humans , Pharmaceutical Preparations/bloodABSTRACT
Local anesthesia block of the inferior alveolar nerve is routinely taught throughout dental education. This commonly used technique eliminates all somatosensory perception of the mandible, mandibular teeth, floor of the mouth, ipsilateral tongue, and all but the lateral (buccal) gingivae. Generally, the dentist or surgeon desires these structures to be anesthetized. However, in the placement of mandibular implants, it may be useful for the patient to be able to sense when the inferior alveolar nerve is in danger of being damaged, possibly producing permanent paresthesia. In this article, the technique of mandibular infiltration prior to mandibular implant placement in the mandible is discussed.
