L-Carnitine (levocarnitine) is a naturally occurring compound found in all mammalian species. The most important biological function of L-carnitine is in the transport of fatty acids into the mitochondria for subsequent β-oxidation, a process which results in the esterification of L-carnitine to form acylcarnitine derivatives. As such, the endogenous carnitine pool is comprised of L-carnitine and various short-, medium- and long-chain acylcarnitines. The physiological importance of L-carnitine and its obligatory role in the mitochondrial metabolism of fatty acids has been clearly established; however, more recently, additional functions of the carnitine system have been described, including the removal of excess acyl groups from the body and the modulation of intracellular coenzyme A (CoA) homeostasis. In light of this, acylcarnitines cannot simply be considered by-products of the enzymatic carnitine transfer system, but provide indirect evidence of altered mitochondrial metabolism. Consequently, examination of the contribution of L-carnitine and acylcarnitines to the endogenous carnitine pool (i.e. carnitine pool composition) is critical in order to adequately characterize metabolic status. The concentrations of L-carnitine and its esters are maintained within relatively narrow limits for normal biological functioning in their pivotal roles in fatty acid oxidation and maintenance of free CoA availability. The homeostasis of carnitine is multifaceted with concentrations achieved and maintained by a combination of oral absorption, de novo biosynthesis, carrier-mediated distribution into tissues and extensive, but saturable, renal tubular reabsorption. Various disorders of carnitine insufficiency have been described but ultimately all result in impaired entry of fatty acids into the mitochondria and consequently disturbed lipid oxidation. Given the sensitivity of acylcarnitine concentrations and the relative carnitine pool composition in reflecting the intramitochondrial acyl-CoA to free CoA ratio (and, hence, any disturbances in mitochondrial metabolism), the relative contribution of L-carnitine and acylcarnitines within the total carnitine pool is therefore considered critical in the identification of mitochondria dysfunction. Although there is considerable research in the literature focused on disorders of carnitine insufficiency, relatively few have examined relative carnitine pool composition in these conditions; consequently, the complexity of these disorders may not be fully understood. Similarly, although important studies have been conducted establishing the pharmacokinetics of exogenous carnitine and short-chain carnitine esters in healthy volunteers, few studies have examined carnitine pharmacokinetics in patient groups. Furthermore, the impact of L-carnitine administration on the kinetics of acylcarnitines has not been established. Given the importance of L-carnitine as well as acylcarnitines in maintaining normal mitochondrial function, this review seeks to examine previous research associated with the...

Long-term hemodialysis treatment is associated with a significant reduction in endogenous plasma and muscle L-carnitine levels and a significant increase in plasma acylcarnitines. The majority of the change in plasma L-carnitine concentrations occurs within the first few months of hemodialysis, while muscle levels continue to decline after 12 months of treatment.

Based on the results of this study, it is recommended that pre- and post-fatigue maximal contraction may be utilised for the assessment of client ability and progression due to their established validity and test-retest reliability. However, previously proposed measures of fatigue such as endurance (duration of sustained contraction), Strength Decrement Index and work performed (function of endurance and force of contraction) are unreliable and invalid and may have limited use in clinical practice.

Therapeutic drug monitoring (TDM) of vancomycin is recommended to improve efficacy, minimize toxicity, and prevent the development of resistant microbial strains. International guidelines now recommend the use of an area under the concentration-time curve (AUC)-guided approach to optimize vancomycin dosing.

Objectives Cefepime-induced neurotoxicity (CIN) has been demonstrated to be associated with cefepime plasma concentrations; however, the toxicity threshold remains unclear. The primary objective of this study was to identify the cefepime plasma trough concentration at which neurotoxicity occurs. Secondary objectives were to determine the incidence of CIN at a large tertiary institution and to identify patient factors associated with the development of CIN. Methods A retrospective review of all adult patients administered cefepime between October 2017 and May 2018 in a tertiary hospital was conducted to determine total incidence of CIN. A receiver operating characteristic (ROC) curve was constructed to review the sensitivity and specificity of using various cefepime trough plasma concentrations to predict the development of neurotoxicity. Cefepime plasma concentrations were measured using ultra-HPLC. A regression was conducted to identify patient factors associated with CIN. Results In total, 206 patients were administered 259 courses of cefepime, with an overall CIN incidence of 6% (16/259 courses). A total of 64 courses had a cefepime trough concentration measured (24.7%). A cefepime trough concentration of 36 mg/L provided the best differentiation between patients who experienced neurotoxicity and those who did not. No other patient covariates were identified to be significantly associated with neurotoxicity occurring. Conclusions A cefepime trough plasma concentration ≥36 mg/L appears to be the most sensitive and specific cut-off to predict CIN occurring. No patient factors were associated with the development of CIN when accounting for cefepime trough plasma concentrations.

Abstract. Reuter SE,

These data illustrate the relationship between carnitine levels and response to rHuEPO treatment in haemodialysis patients, in particular, the importance of the proportion of long-chain acylcarnitines within the plasma carnitine pool. This proportion may be more indicative of the response to L-carnitine supplementation than absolute L-carnitine levels alone.

These results are useful in the evaluation of biochemical or metabolic disturbances and in the diagnosis and treatment of patients with carnitine deficiency.