Lactic acidosis buformin

In Spain a 69-year-old woman with a dilated cardiomyopathy and poor inferior ventricular function developed lactic acidosis after an increase in the dose of buformin (pH 7.1, lactate 18 mmol/1). After withdrawal of buformin and infusion of sodium bicarbonate her renal function and electrolyte disturbances were corrected (61). 

In patients taking metformin, lactic acidosis is rare (3 per 100 000 patient-years) and is most often seen when contraindications to metformin (impaired kidney or liver function, alcoholism, circulatory problems, old age) are neglected or not detected (64). Although the relative risk of lactic acidosis with metformin is significantly lower than with phenformin or buformin (65), it has been repeatedly reported (SEDA-6, 371) (66), even in the absence of known contraindications (67). 

Mechanism and susceptibility factors Biguanides in high doses inhibit the oxidation of carbohydrate substrates by affecting mitochondrial function. Anoxidative carbohydrate metabolism stimulates the production of lactate. High lactate production leads to lactic acidosis (type B) with a low pH (<6.95). Hyperlactatemia was common in patients taking buformin, even without alcoholism or impaired liver, kidney, or cardiac function (70). 

The results of hemodialysis in biguanide-induced lactic acidosis are variable. Metformin and buformin are dialy-sable, but phenformin is poorly eliminated. Successful continuous venovenous hemofiltration has been reported (81). 

Tamura Y, Tsukamoto K, Yakamoto N, Ishibashi S, Kadowaki T, Kimura S. A case of buformin treated type 2 diabetes mellitus without any other underlying disease complicated by acute renal failure, lactic acidosis, subsequent diarrhea and vomiting [Japanese]. Tonyobyo 2003 46 325-7. 

Kurita S, Muramoto S, Okabe G. A case of lactic acidosis acute renal failure caused by taking a lot of buformin for suicide [Japanese], Tonyobyo 2003 46 329-31. 

An 84-year-old diabetic died 6 hours after admission to hospital with severe lactic acidosis caused by buformin. The plasma concentration on admission was 5.5 gg/ml. Postmortem tissue concentrations were plasma 3.2 gg/ml, bile 6.3 gg/ml, heart 3.0 gg/g, kidney 98 ig/g, liver 5.2 gg/g, lung 2.8 gg/g (G. de Groot et al., J. analyt. Toxicol., 1980, 4, 281-285). 

Metformin (Glucophage, others) and phenformin were introduced in 1957, and buformin was introduced in 1958. The latter was of limited use, but metformin and phenformin were used widely. Phenformin was withdrawn in many countries during the 1970s because of an association with lactic acidosis. Metformin has been associated only rarely with that complication, and has been used widely in Europe and Canada it became available in the United States in 1995. Metformin given alone or in combination with a sulfonylurea improves glycemic control and lipid concentrations in patients who respond poorly to diet or to a sulfonylurea alone. 

Lowering of blood glucose by the infusion of guanidine [89], biguanides and two linked guanidine moieties has proved to be useful for the treatment of diabetes meUims. Three compounds became available for diabetes therapy, phenformin (51), buformin (52) and metformin (53) (Figure 10.12). Phenformin (51) was withdrawn due to lactic acidosis [90]. Metformin (53), a less lipophilic biguanide, was recently approved for use in the USA after 20 years of use in Europe [91]. 

The literature on the 3 most widely used biguanides, i.e. buformin, metformin and phenformin, continues to produce reports of lactic acidosis, mostly after phenformin (59 ). However, buformin (60 ) and excessive use of metformin (61 ) can also cause lactic acidosis. The complication is mostly seen in older patients, but a case has been reported involving a 30-year-old phenformin-treated patient with normal cardiac and renal function, who received tetracycline for fever and cervical adenopathy (62 ). 

It is not clear if this opinion must also be extended to the other biguanides. Less cases of lactic acidosis are reported after buformin or metformin therapy. Czyzyk (81 ), in a study on increases in lactate levels induced by alcohol or fructose after pretreatment with biguanides, found a rise in lactate levels for all types of biguanides. Th re is no indication that buformin or metformin will prove more beneficial if they are compared with phenformin. 

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