| Popis: |
The disposition of drugs may be influenced by hyperbaric conditions, in particular by changes of liver perfusion. The effect of hyperbaric hyperoxia on the pharmacokinetics of lidocaine, a drug eliminated in the liver with a perfusion-limited clearance, was investigated in human volunteers in a crossover trial.A single dose lidocaine i.v. bolus (0.69 or 0.75 mg x kg(-1)) was administered to two volunteers under normobaric conditions (NB: 1 bar or 0.1 MPa, air) and under hyperbaric/hyperoxic conditions (HBO: 2.5 bar or 0.25 MPa, alternating 100% O2-breathing for 20 min and air breathing for 5 min). Blood samples were serially collected for 5 h (NB) or 75 min (HBO), and lidocaine concentration in serum was measured by immunoassay. Data were analyzed assuming linear kinetics and an open two-compartment model.At 1 bar or 0.1 MPa, lidocaine injection caused only slight dizziness and buzzing in the ear. Heart rate and blood pressure were not influenced. Under HBO, lidocaine injection caused marked dizziness and buzzing in the ears, sweating, tremor and coordination-disturbances, even though maximal lidocaine concentrations (0.63 mg x L(-1) and 0.70 mg x L(-1)) were far below therapeutic serum concentrations (1.5-5.0 mg x L(-1)). Pharmacokinetic parameters of lidocaine were similar to those published earlier (T1/2beta: 110+/-16 min; CI: 12.6+/-2.9 ml x min(-1) x kg(-1); Vss: 1.73+/-0.18 L x kg(-1)). There was no indication for effects of HBO on the disposition of lidocaine (p0.05).The pharmacokinetics of lidocaine do not seem to be influenced in a clinically relevant way in humans by a single HBO-exposure under usual therapeutic conditions. Side effects of lidocaine at 2.5 bar or 0.25 MPa may be caused by pharmacodynamic interactions between lidocaine and hyperbaric/hyperoxic conditions. |
