The effect of age on pharmacokinetics of the local anesthetic drug articaine.

Institute of Clinical Pharmacology, Faculty of Medicine, Technical University, Dresden, Germany.
Regional Anesthesia and Pain Medicine (Impact Factor: 3.46). 01/1999; 24(6):524-8. DOI: 10.1016/S1098-7339(99)90043-3
Source: PubMed

ABSTRACT With increasing age, there are physiologic changes that could affect pharmacokinetics of drugs. More elderly patients are undergoing routine dental procedures for which local anesthesia could be required. The goal of the present study was to evaluate the effect of age on pharmacokinetics of the local anesthetic agent articaine.
The submucosal infiltration anesthesia from two different dosages of 4% articaine without epinephrine was compared in healthy elderly and young volunteers. High performance liquid chromatography has been used to determine concentrations of articaine in serum. Basic pharmacokinetic parameters were calculated according to standard procedures using a two-exponent equation.
The clearance and volume of distribution (Vdss) of articaine after infiltration anesthesia were significantly lower in elderly volunteers compared with young volunteers. The area under the serum concentration-time curve and maximum drug concentration (Cmax) values did not differ significantly with age; however, both parameters tended to be higher in elderly volunteers. No changes in terminal half-life and time to reach maximum serum concentration (t(max)) were observed. The Cmax and tmax values of the metabolite articainic acid were similar in young and elderly volunteers. CONCLUSIONS The results show that the metabolism of articaine is age-independent in healthy male volunteers. The smaller Vdss in the elderly results in a trend to higher serum levels after a given dose of articaine. No change of dosage of articaine in elderly patients should be necessary.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Local anaesthetics have been shown to exert pronounced cardiodepressant effects after intravenous administration in high doses. Thus, we compared the cardiovascular effects of articaine with those of lidocaine and placebo after submucous administration in healthy volunteers during bicycle exercise ergometry. A single-blind, randomised, placebo-controlled, crossover study design with washout periods of 1 week each between the three treatment days was used. Articaine 40mg (A), lidocaine 40mg (L) and placebo (P) were injected submucously in the upper jaw in 12 healthy male volunteers who had had cardiovascular diseases excluded. Parameters measured at baseline and at 15 minutes, 60 minutes and 105 minutes were systolic blood pressure (BP) and heart rate at 50W, 100W and 150W, and cardiac output at 100W. Tolerability was assessed by ECG measurements and through reporting of adverse events. 15 minutes after drug administration, cardiac output was reduced by -3.8% (P), -6.8% (A), and -4.2% (L) [difference between groups was not significant]. There were also no statistically significant differences between groups for cardiac output at 60 and 105 minutes, or for all BP and heart rate measurements. Neither drug exhibited significant effects on selected cardiovascular parameters during submaximal exercise when compared with placebo.
    Clinical Drug Investigation 02/2003; 23(4):219-23. · 1.70 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Articaine is an intermediate-potency, short-acting amide local anesthetic with a fast metabolism due to an ester group in its structure. It is effective with local infiltration or peripheral nerve block in dentistry, when administered as a spinal, epidural, ocular, or regional nerve block, or when injected intravenously for regional anesthesia. In comparative trials, its clinical effects were not generally significantly different from those of other short-acting local anesthetics like lidocaine, prilocaine, and chloroprocaine, and there is no conclusive evidence demonstrating above-average neurotoxicity. Articaine proved to be suitable and safe for procedures requiring a short duration of action in which a fast onset of anesthesia is desired, eg, dental procedures and ambulatory spinal anesthesia, in normal and in special populations.
    Local and Regional Anesthesia 01/2012; 5:23-33.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ageing is associated with a decline in drug elimination; hence, using the same doses as in younger adults may result in higher plasma drug concentrations and toxicity. Two approaches are available for dose correction to account for decreased drug elimination. One procedure is based on the extrarenal elimination fraction (Q(0)) and the age-dependent changes in creatinine clearance; the other uses the decline in total drug clearance (CL). Mean values of Q(0) and CL in young and old people are reported for many drugs in the literature and are summarised in this article. Although the pharmacokinetic techniques for dose adjustment in the elderly are useful, they provide only an average dose correction and neglect age-dependent changes in drug bio-availability, plasma protein binding, the fate of active metabolites, and altered sensitivity to drugs. To account for pharmacodynamic changes in old age, clinical and/or biochemical targets should be defined as therapeutic goals. Drugs whose effects cannot be monitored in these terms should be avoided in elderly individuals.
    Expert Opinion on Drug Metabolism &amp Toxicology 07/2005; 1(1):33-48. · 2.94 Impact Factor