Lidocaine pharmacokinetics during hyperbaric hyperoxia in humans.

METHODS: 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. METHODS: 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. RESULTS: 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 (p > 0.05). CONCLUSION: 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.

Effects of hyperbaric and hyperoxic conditions on the disposition of drugs: theoretical considerations and a review of the literature.

1. Hyperbaric or hyperoxic or both conditions may affect the disposition of drugs by (1) changes in the catalytic activity of drug metabolizing enzymes, (2) hemodynamic changes and (3) changes in membrane permeability, affecting drug distribution. 2. In isolated microsome preparations from rat liver, the metabolism rate of aniline, but not of amidopirin, is reduced by hyperoxia. In vivo, the clearance of salicylic acid is enhanced in the dog at 2.8 ATA and 100% O2, but not at 6 ATA and air, for reasons that are still unknown. The disposition of theophylline, pentobarbital or pethidine is not affected in dogs by hyperbaric or hyperoxic conditions. 3. In human volunteers, hyperbaric or hyperoxic or both conditions do not affect the disposition of gentamycin (2.4 bar, 100% O2), caffeine or lidocaine (2.5 bar, 100% O2). 4. In conclusion, a single exposure to hyperbaric or hyperoxic conditions does not seem to affect single-dose pharmacokinetics of drugs eliminated by the kidney (gentamycin) or by the liver with a capacity-limited clearance (pentobarbital, theophylline, caffeine) or with a perfusion-limited clearance (pethidine, lidocaine). The enhancement of salicylic acid clearance in dogs under hyperoxic conditions remains unclear.

Caffeine pharmacokinetics during hyperbaric hyperoxia in humans.

The effect of hyperbaric hyperoxia on the pharmacokinetics of caffeine was investigated in human volunteers. Some 600 ml of coffee were administered to 2 volunteers and blood samples were serially collected for 24 h. The volunteers entered a hyperbaric chamber 2.5 h following coffee ingestion for a total period of 110 min (0.25 MPa, alternating 100% O2-breathing for 20 min and air breathing for 5 min). The concentrations of caffeine in serum was determined by high pressure liquid chromatography. The caffeine amount ingested was determined by analyzing an aliquot of the coffee beverage. Data were analyzed assuming linear kinetics and an open one-compartment model. Effects of hyperbaric hyperoxia on caffeine disposition were investigated using a runs test. Moreover, a one-population t-test was applied to residuals, separately for data from the initial normobaric period, the hyperbaric period and the terminal normobaric period. Pharmacokinetic parameters were similar to established literature data on caffeine [Volunteer 1: maximal concentration (Cmax: 6.13 mg.L-1 at Tmax: 55 min, half-time of elimination (T1/2: 180 min, total clearance (Cl): 3.41 ml.min-1.kg-1; volume of distribution (Vd: 0.88 I.kg-1; Volunteer 2: Cmax: 6.23 mg.L-1, Tmax: 94 min, T1/2: 283 min, Cl: 1.90 ml.min-1.kg-1, Vd: 0.77 L.kg-1). The runs test as well as the analysis of residuals gave no evidence for alterations of caffeine disposition by hyperoxia (p > 0.05). The pharmacokinetics of caffeine do not seem to be influenced in a clinically relevant way in humans during a stay for 100 min at 0.25 MPa, alternating 100% O2 and air breathing.