In this review we analyzed the pharmacokinetic basis for high dose treatment with antibiotics of patients with cystic fibrosis. Both our results and those from other well designed pharmacokinetic studies do not support the view that low blood levels of antibacterials are a common feature of CF. We were unable to detect a decrease in absorption, nor could we find evidence for enhanced elimination of antibacterials in CF. Both these factors have been considered responsible for reducing the plasma (and tissue) levels of antibiotics. Most recent studies on kidney function are in agreement with these findings, since neither inulin nor creatinine clearance differ between CF-patients and healthy volunteers. In contrast to previous discussion, the volume of distribution (Vdss) was not elevated for any compound. The rational of weight correction of volume terms like Vdss or total clearance has never been clearly demonstrated and should therefore not be used without prior proof of relevance. Since the variability of pharmacokinetic parameters of antibiotics in CF-patients may be considerable, we suggest that a dose increase of 20-30% may be justified, but cannot agree with two to fourfold increases in dosage as previously proposed and applied in many CF-centers. Until more findings become available for non-adult CF-patients, these conclusions are only valid for adult CF-patients.

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Subacute necrotizing encephalomyelopathy (SNE) has been observed in an infant with regressing psychomotor development. The concentrations of alanine, pyruvate and lactate were increased in the serum and blood as well as in the cerebrospinal fluid. Pyruvate carboxylase activity was reduced in the liver tissue. An inhibitor of thiamine-pyrophosphate-ATP-phosphotransferase was present in the urine. Thiamine treatment was followed by a decrease of serum alanine and blood pyruvate and lactate, but there was no clinical improvement during a period of 17 months. Ultrastructural investigations revealed high glycogen levels in liver tissue and skeletal muscle. These findings contrast with decreased gluconeogenesis, which is suggested by the diminished pyruvate carboxylase activity. Therefore it is concluded that reduced hepatic pyruvate carboxylase activity is not the primary cause of SNE.

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The vitamin K-dependent carboxylation of the prothrombin precursor PIVKA II (protein induced by vitamin K absence analogous to Factor II) is essential for the synthesis of prothrombin. The noncarboxylated precursor is found in peripheral blood in the presence of vitamin K deficiency. In this study prothrombin time, Factor II and Factor VII activity, and PIVKA II were investigated in 57 newborns without vitamin K prophylaxis in order to assess their vitamin K status. Two-dimensional immunoelectrophoresis demonstrated the presence of PIVKA II in 21% of the newborns, predominantly on the second day. The PIVKA-II positive group showed significantly lower prothrombin times than the PIVKA II-negative group. An oral dose of 3 mg vitamin K (Konakion) was administered to 35 healthy newborns in a second group with the first feeding. On the second day of life, these infants showed significantly higher vitamin K-dependent laboratory parameters than the group not given vitamin K; only 9% of the treated infants were positive for PIVKA II.