Cefamandole levels during thoracoabdominal aortic aneurysm surgery.

The pharmacokinetics of prophylactic antibodies may differ in cardiac and aortic aneurysm surgery for at least two reasons: aortic aneurysm surgery generally entails a greater blood volume loss and replacement, and aortic aneurysm surgery usually does not require extracorporeal cardiopulmonary bypass. We prospectively studied two different cefamandole dosing regimens in patients undergoing aortic aneurysm surgery (phase 1, 1 gm intravenously at the induction of anesthesia; phase 2, 2 gm intravenously at the induction of anesthesia followed by 1 gm intravenously every 2 hours during surgery). In phase 1 and 2 plasma levels were measured at the time of skin incision, aortic cross-clamping, aortic unclamping, and skin closure. In phase 2 cefamandole elimination in urine and cell-saver effluent was also determined. An adequate plasma level of 10 micrograms/ml was maintained in only 4 of 14 patients in phase 1, but in 10 of 10 patients in phase 2. Cefamandole loss in cell-saver effluent was 136 +/- 100 mg, which was 13% of the measured renally excreted amount. As has been previously shown in cardiac surgery, a cefamandole prophylactic antibiotic regimen of 2 gm intravenously at the induction of anesthesia followed by 1 gm every 2 hours during surgery provides a dependable and practical dosing regimen in patients undergoing aortic aneurysm surgery.

Bioavailability and pharmacokinetics of ofloxacin in healthy volunteers.

The pharmacokinetics and bioavailability of ofloxacin in 20 healthy male volunteers were studied in an open-label, randomized, two-way crossover study. Ofloxacin (400 mg) was administered either as a 1-h infusion or as an oral tablet. The mean peak concentration after intravenous infusion was 4.30 +/- 0.69 microgram/ml, and that after oral administration was 3.14 +/- 0.53 microgram/ml, occurring 1.74 +/- 0.57 h after dosing. The bioavailability (F) of the oral dosage form of ofloxacin was virtually identical to that of the intravenous form (F = 105% +/- 7%). This complete bioavailability of ofloxacin is supportive of the use of the oral dosage form for the treatment of infections in hospitalized patients either as a replacement for intravenous ofloxacin therapy or in streamlining therapy from the intravenous to the oral route.

Absorption of ciprofloxacin administered through a nasogastric or a nasoduodenal tube in volunteers and patients receiving enteral nutrition.

The absorption of ciprofloxacin was higher when administered through a nasoduodenal tube than through a nasogastric tube, indicating that even though acidic gastric pH is needed for rapid disintegration, dissolved ciprofloxacin might not be stable in the gastric environment. If the length of exposure or the different gastric environment in each individual affects the overall absorption of ciprofloxacin, this could explain the reported variability in ciprofloxacin absorption and suggests the need for the development of an enteric-coated tablet. Further studies are needed to fully characterize the absorption of ciprofloxacin in patients with different illnesses, gastric transit times, gastrointestinal environments and of different ages.

Clinical pharmacokinetics of ceftriaxone.

Ceftriaxone is a third-generation cephalosporin that exhibits saturable plasma protein binding, which influences its pharmacokinetic parameters depending on the dose. Systemic clearance and volume of distribution of total drug show dependence on both concentration and time, whereas for unbound drug these parameters remain constant. The decrease in renal or non-renal clearance with age or in the presence of disease states is often compensated by the concurrent increase in free fraction, resulting in no apparent changes in half-life and no need for dose adjustment. Because of its unusually long plasma half-life, the availability of intramuscular administration and its high intrinsic activity against many organisms, ceftriaxone has become a popular agent in once-daily therapy of infections in paediatric patients, gonococcal infections and outpatient management of pneumonia and osteomyelitis.

Relative bioavailability in healthy volunteers of ciprofloxacin administered through a nasogastric tube with and without enteral feeding.

The bioavailability of ciprofloxacin after its administration through a nasogastric (NG) feeding tube was studied in six healthy volunteers. Each subject received, on separate occasions, an intact 750-mg ciprofloxacin tablet, a crushed tablet as a suspension through an NG tube, and a crushed tablet as a suspension through an NG tube while receiving enteral feeding. No statistically significant differences were observed in the area under the curve, maximum concentration in serum, and time to peak concentration among these three modes of administration. These findings suggest that ciprofloxacin is well absorbed after administration via an NG tube (compared with an orally administered intact tablet) even in the presence of enteral feeding.